Intravenous immunoglobulin mediates anti-inflammatory effects in peripheral blood mononuclear cells by inducing autophagy.
Identifieur interne : 000100 ( Main/Exploration ); précédent : 000099; suivant : 000101Intravenous immunoglobulin mediates anti-inflammatory effects in peripheral blood mononuclear cells by inducing autophagy.
Auteurs : Mrinmoy Das [France] ; Anupama Karnam [France] ; Emmanuel Stephen-Victor [France] ; Laurent Gilardin [France] ; Bharat Bhatt [Inde] ; Varun Kumar Sharma [France] ; Naresh Rambabu [France] ; Veerupaxagouda Patil [France] ; Maxime Lecerf [France] ; Fabian K Sermann [Suisse] ; Patrick Bruneval [France] ; Kithiganahalli Narayanaswamy Balaji [Inde] ; Olivier Benveniste [France] ; Srini V. Kaveri [France] ; Jagadeesh Bayry [France]Source :
- Cell death & disease [ 2041-4889 ] ; 2020.
Abstract
Autophagy plays an important role in the regulation of autoimmune and autoinflammatory responses of the immune cells. Defective autophagy process is associated with various autoimmune and inflammatory diseases. Moreover, in many of these diseases, the therapeutic use of normal immunoglobulin G or intravenous immunoglobulin (IVIG), a pooled normal IgG preparation, is well documented. Therefore, we explored if IVIG immunotherapy exerts therapeutic benefits via induction of autophagy in the immune cells. Here we show that IVIG induces autophagy in peripheral blood mononuclear cells (PBMCs). Further dissection of this process revealed that IVIG-induced autophagy is restricted to inflammatory cells like monocytes, dendritic cells, and M1 macrophages but not in cells associated with Th2 immune response like M2 macrophages. IVIG induces autophagy by activating AMP-dependent protein kinase, beclin-1, class III phosphoinositide 3-kinase and p38 mitogen-activated protein kinase and by inhibiting mammalian target of rapamycin. Mechanistically, IVIG-induced autophagy is F(ab')2-dependent but sialylation independent, and requires endocytosis of IgG by innate cells. Inhibition of autophagy compromised the ability of IVIG to suppress the inflammatory cytokines in innate immune cells. Moreover, IVIG therapy in inflammatory myopathies such as dermatomyositis, antisynthetase syndrome and immune-mediated necrotizing myopathy induced autophagy in PBMCs and reduced inflammatory cytokines in the circulation, thus validating the translational importance of these results. Our data provide insight on how circulating normal immunoglobulins maintain immune homeostasis and explain in part the mechanism by which IVIG therapy benefits patients with autoimmune and inflammatory diseases.
DOI: 10.1038/s41419-020-2249-y
PubMed: 31974400
PubMed Central: PMC6978335
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Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Stephen Victor, Emmanuel" sort="Stephen Victor, Emmanuel" uniqKey="Stephen Victor E" first="Emmanuel" last="Stephen-Victor">Emmanuel Stephen-Victor</name><affiliation wicri:level="3"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale; 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Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Rambabu, Naresh" sort="Rambabu, Naresh" uniqKey="Rambabu N" first="Naresh" last="Rambabu">Naresh Rambabu</name><affiliation wicri:level="3"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Patil, Veerupaxagouda" sort="Patil, Veerupaxagouda" uniqKey="Patil V" first="Veerupaxagouda" last="Patil">Veerupaxagouda Patil</name><affiliation wicri:level="3"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Lecerf, Maxime" sort="Lecerf, Maxime" uniqKey="Lecerf M" first="Maxime" last="Lecerf">Maxime Lecerf</name><affiliation wicri:level="3"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Université Paris Descartes, Sorbonne Paris Cité, 75006, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université Paris Descartes, Sorbonne Paris Cité, 75006, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Paris-Descartes</orgName></affiliation></author><author><name sortKey="K Sermann, Fabian" sort="K Sermann, Fabian" uniqKey="K Sermann F" first="Fabian" last="K Sermann">Fabian K Sermann</name><affiliation wicri:level="3"><nlm:affiliation>CSL Behring, Research, CSL Biologics Research Center, 3014, Bern, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>CSL Behring, Research, CSL Biologics Research Center, 3014, Bern</wicri:regionArea><placeName><settlement type="city">Berne</settlement><region type="région" nuts="3">Canton de Berne</region></placeName></affiliation></author><author><name sortKey="Bruneval, Patrick" sort="Bruneval, Patrick" uniqKey="Bruneval P" first="Patrick" last="Bruneval">Patrick Bruneval</name><affiliation wicri:level="3"><nlm:affiliation>Service d'anatomie pathologique, Hôpital Européen Georges Pompidou, 75015, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service d'anatomie pathologique, Hôpital Européen Georges Pompidou, 75015, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Narayanaswamy Balaji, Kithiganahalli" sort="Narayanaswamy Balaji, Kithiganahalli" uniqKey="Narayanaswamy Balaji K" first="Kithiganahalli" last="Narayanaswamy Balaji">Kithiganahalli Narayanaswamy Balaji</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, 560012, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, 560012</wicri:regionArea><wicri:noRegion>560012</wicri:noRegion></affiliation></author><author><name sortKey="Benveniste, Olivier" sort="Benveniste, Olivier" uniqKey="Benveniste O" first="Olivier" last="Benveniste">Olivier Benveniste</name><affiliation wicri:level="3"><nlm:affiliation>Département de Médecine Interne et Immunologie Clinique, Hôpital Pitié-Salpêtrière, AP-HP, 75013, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Département de Médecine Interne et Immunologie Clinique, Hôpital Pitié-Salpêtrière, AP-HP, 75013, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale Unité 974, Sorbonne Université, 75013, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale Unité 974, Sorbonne Université, 75013, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Kaveri, Srini V" sort="Kaveri, Srini V" uniqKey="Kaveri S" first="Srini V" last="Kaveri">Srini V. Kaveri</name><affiliation wicri:level="3"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Université Paris Descartes, Sorbonne Paris Cité, 75006, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université Paris Descartes, Sorbonne Paris Cité, 75006, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Paris-Descartes</orgName></affiliation></author><author><name sortKey="Bayry, Jagadeesh" sort="Bayry, Jagadeesh" uniqKey="Bayry J" first="Jagadeesh" last="Bayry">Jagadeesh Bayry</name><affiliation wicri:level="3"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris, France. jagadeesh.bayry@crc.jussieu.fr.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Université Paris Descartes, Sorbonne Paris Cité, 75006, Paris, France. jagadeesh.bayry@crc.jussieu.fr.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université Paris Descartes, Sorbonne Paris Cité, 75006, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Paris-Descartes</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:31974400</idno><idno type="pmid">31974400</idno><idno type="doi">10.1038/s41419-020-2249-y</idno><idno type="pmc">PMC6978335</idno><idno type="wicri:Area/Main/Corpus">000131</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000131</idno><idno type="wicri:Area/Main/Curation">000131</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000131</idno><idno type="wicri:Area/Main/Exploration">000131</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Intravenous immunoglobulin mediates anti-inflammatory effects in peripheral blood mononuclear cells by inducing autophagy.</title><author><name sortKey="Das, Mrinmoy" sort="Das, Mrinmoy" uniqKey="Das M" first="Mrinmoy" last="Das">Mrinmoy Das</name><affiliation wicri:level="3"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Karnam, Anupama" sort="Karnam, Anupama" uniqKey="Karnam A" first="Anupama" last="Karnam">Anupama Karnam</name><affiliation wicri:level="3"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Stephen Victor, Emmanuel" sort="Stephen Victor, Emmanuel" uniqKey="Stephen Victor E" first="Emmanuel" last="Stephen-Victor">Emmanuel Stephen-Victor</name><affiliation wicri:level="3"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Gilardin, Laurent" sort="Gilardin, Laurent" uniqKey="Gilardin L" first="Laurent" last="Gilardin">Laurent Gilardin</name><affiliation wicri:level="3"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Département de Médecine Interne et Immunologie Clinique, Hôpital Pitié-Salpêtrière, AP-HP, 75013, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Département de Médecine Interne et Immunologie Clinique, Hôpital Pitié-Salpêtrière, AP-HP, 75013, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Bhatt, Bharat" sort="Bhatt, Bharat" uniqKey="Bhatt B" first="Bharat" last="Bhatt">Bharat Bhatt</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, 560012, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, 560012</wicri:regionArea><wicri:noRegion>560012</wicri:noRegion></affiliation></author><author><name sortKey="Kumar Sharma, Varun" sort="Kumar Sharma, Varun" uniqKey="Kumar Sharma V" first="Varun" last="Kumar Sharma">Varun Kumar Sharma</name><affiliation wicri:level="3"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Rambabu, Naresh" sort="Rambabu, Naresh" uniqKey="Rambabu N" first="Naresh" last="Rambabu">Naresh Rambabu</name><affiliation wicri:level="3"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Patil, Veerupaxagouda" sort="Patil, Veerupaxagouda" uniqKey="Patil V" first="Veerupaxagouda" last="Patil">Veerupaxagouda Patil</name><affiliation wicri:level="3"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Lecerf, Maxime" sort="Lecerf, Maxime" uniqKey="Lecerf M" first="Maxime" last="Lecerf">Maxime Lecerf</name><affiliation wicri:level="3"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Université Paris Descartes, Sorbonne Paris Cité, 75006, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université Paris Descartes, Sorbonne Paris Cité, 75006, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Paris-Descartes</orgName></affiliation></author><author><name sortKey="K Sermann, Fabian" sort="K Sermann, Fabian" uniqKey="K Sermann F" first="Fabian" last="K Sermann">Fabian K Sermann</name><affiliation wicri:level="3"><nlm:affiliation>CSL Behring, Research, CSL Biologics Research Center, 3014, Bern, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>CSL Behring, Research, CSL Biologics Research Center, 3014, Bern</wicri:regionArea><placeName><settlement type="city">Berne</settlement><region type="région" nuts="3">Canton de Berne</region></placeName></affiliation></author><author><name sortKey="Bruneval, Patrick" sort="Bruneval, Patrick" uniqKey="Bruneval P" first="Patrick" last="Bruneval">Patrick Bruneval</name><affiliation wicri:level="3"><nlm:affiliation>Service d'anatomie pathologique, Hôpital Européen Georges Pompidou, 75015, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service d'anatomie pathologique, Hôpital Européen Georges Pompidou, 75015, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Narayanaswamy Balaji, Kithiganahalli" sort="Narayanaswamy Balaji, Kithiganahalli" uniqKey="Narayanaswamy Balaji K" first="Kithiganahalli" last="Narayanaswamy Balaji">Kithiganahalli Narayanaswamy Balaji</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, 560012, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, 560012</wicri:regionArea><wicri:noRegion>560012</wicri:noRegion></affiliation></author><author><name sortKey="Benveniste, Olivier" sort="Benveniste, Olivier" uniqKey="Benveniste O" first="Olivier" last="Benveniste">Olivier Benveniste</name><affiliation wicri:level="3"><nlm:affiliation>Département de Médecine Interne et Immunologie Clinique, Hôpital Pitié-Salpêtrière, AP-HP, 75013, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Département de Médecine Interne et Immunologie Clinique, Hôpital Pitié-Salpêtrière, AP-HP, 75013, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale Unité 974, Sorbonne Université, 75013, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale Unité 974, Sorbonne Université, 75013, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Kaveri, Srini V" sort="Kaveri, Srini V" uniqKey="Kaveri S" first="Srini V" last="Kaveri">Srini V. Kaveri</name><affiliation wicri:level="3"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Université Paris Descartes, Sorbonne Paris Cité, 75006, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université Paris Descartes, Sorbonne Paris Cité, 75006, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Paris-Descartes</orgName></affiliation></author><author><name sortKey="Bayry, Jagadeesh" sort="Bayry, Jagadeesh" uniqKey="Bayry J" first="Jagadeesh" last="Bayry">Jagadeesh Bayry</name><affiliation wicri:level="3"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris, France. jagadeesh.bayry@crc.jussieu.fr.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Université Paris Descartes, Sorbonne Paris Cité, 75006, Paris, France. jagadeesh.bayry@crc.jussieu.fr.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université Paris Descartes, Sorbonne Paris Cité, 75006, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Paris-Descartes</orgName></affiliation></author></analytic><series><title level="j">Cell death & disease</title><idno type="eISSN">2041-4889</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Autophagy plays an important role in the regulation of autoimmune and autoinflammatory responses of the immune cells. Defective autophagy process is associated with various autoimmune and inflammatory diseases. Moreover, in many of these diseases, the therapeutic use of normal immunoglobulin G or intravenous immunoglobulin (IVIG), a pooled normal IgG preparation, is well documented. Therefore, we explored if IVIG immunotherapy exerts therapeutic benefits via induction of autophagy in the immune cells. Here we show that IVIG induces autophagy in peripheral blood mononuclear cells (PBMCs). Further dissection of this process revealed that IVIG-induced autophagy is restricted to inflammatory cells like monocytes, dendritic cells, and M1 macrophages but not in cells associated with Th2 immune response like M2 macrophages. IVIG induces autophagy by activating AMP-dependent protein kinase, beclin-1, class III phosphoinositide 3-kinase and p38 mitogen-activated protein kinase and by inhibiting mammalian target of rapamycin. Mechanistically, IVIG-induced autophagy is F(ab')<sub>2</sub>-dependent but sialylation independent, and requires endocytosis of IgG by innate cells. Inhibition of autophagy compromised the ability of IVIG to suppress the inflammatory cytokines in innate immune cells. Moreover, IVIG therapy in inflammatory myopathies such as dermatomyositis, antisynthetase syndrome and immune-mediated necrotizing myopathy induced autophagy in PBMCs and reduced inflammatory cytokines in the circulation, thus validating the translational importance of these results. Our data provide insight on how circulating normal immunoglobulins maintain immune homeostasis and explain in part the mechanism by which IVIG therapy benefits patients with autoimmune and inflammatory diseases.</div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">31974400</PMID><DateRevised><Year>2020</Year><Month>06</Month><Day>11</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2041-4889</ISSN><JournalIssue CitedMedium="Internet"><Volume>11</Volume><Issue>1</Issue><PubDate><Year>2020</Year><Month>01</Month><Day>23</Day></PubDate></JournalIssue><Title>Cell death & disease</Title><ISOAbbreviation>Cell Death Dis</ISOAbbreviation></Journal><ArticleTitle>Intravenous immunoglobulin mediates anti-inflammatory effects in peripheral blood mononuclear cells by inducing autophagy.</ArticleTitle><Pagination><MedlinePgn>50</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/s41419-020-2249-y</ELocationID><Abstract><AbstractText>Autophagy plays an important role in the regulation of autoimmune and autoinflammatory responses of the immune cells. Defective autophagy process is associated with various autoimmune and inflammatory diseases. Moreover, in many of these diseases, the therapeutic use of normal immunoglobulin G or intravenous immunoglobulin (IVIG), a pooled normal IgG preparation, is well documented. Therefore, we explored if IVIG immunotherapy exerts therapeutic benefits via induction of autophagy in the immune cells. Here we show that IVIG induces autophagy in peripheral blood mononuclear cells (PBMCs). Further dissection of this process revealed that IVIG-induced autophagy is restricted to inflammatory cells like monocytes, dendritic cells, and M1 macrophages but not in cells associated with Th2 immune response like M2 macrophages. IVIG induces autophagy by activating AMP-dependent protein kinase, beclin-1, class III phosphoinositide 3-kinase and p38 mitogen-activated protein kinase and by inhibiting mammalian target of rapamycin. Mechanistically, IVIG-induced autophagy is F(ab')<sub>2</sub>-dependent but sialylation independent, and requires endocytosis of IgG by innate cells. Inhibition of autophagy compromised the ability of IVIG to suppress the inflammatory cytokines in innate immune cells. Moreover, IVIG therapy in inflammatory myopathies such as dermatomyositis, antisynthetase syndrome and immune-mediated necrotizing myopathy induced autophagy in PBMCs and reduced inflammatory cytokines in the circulation, thus validating the translational importance of these results. Our data provide insight on how circulating normal immunoglobulins maintain immune homeostasis and explain in part the mechanism by which IVIG therapy benefits patients with autoimmune and inflammatory diseases.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Das</LastName><ForeName>Mrinmoy</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Karnam</LastName><ForeName>Anupama</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Stephen-Victor</LastName><ForeName>Emmanuel</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gilardin</LastName><ForeName>Laurent</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Département de Médecine Interne et Immunologie Clinique, Hôpital Pitié-Salpêtrière, AP-HP, 75013, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bhatt</LastName><ForeName>Bharat</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, 560012, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kumar Sharma</LastName><ForeName>Varun</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rambabu</LastName><ForeName>Naresh</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Patil</LastName><ForeName>Veerupaxagouda</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lecerf</LastName><ForeName>Maxime</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Université Paris Descartes, Sorbonne Paris Cité, 75006, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Käsermann</LastName><ForeName>Fabian</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>CSL Behring, Research, CSL Biologics Research Center, 3014, Bern, Switzerland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bruneval</LastName><ForeName>Patrick</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Service d'anatomie pathologique, Hôpital Européen Georges Pompidou, 75015, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Narayanaswamy Balaji</LastName><ForeName>Kithiganahalli</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, 560012, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Benveniste</LastName><ForeName>Olivier</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>Département de Médecine Interne et Immunologie Clinique, Hôpital Pitié-Salpêtrière, AP-HP, 75013, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institut National de la Santé et de la Recherche Médicale Unité 974, Sorbonne Université, 75013, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kaveri</LastName><ForeName>Srini V</ForeName><Initials>SV</Initials><AffiliationInfo><Affiliation>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Université Paris Descartes, Sorbonne Paris Cité, 75006, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bayry</LastName><ForeName>Jagadeesh</ForeName><Initials>J</Initials><Identifier Source="ORCID">0000-0003-0498-9808</Identifier><AffiliationInfo><Affiliation>Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe- Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, 75006, Paris, France. jagadeesh.bayry@crc.jussieu.fr.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Université Paris Descartes, Sorbonne Paris Cité, 75006, Paris, France. jagadeesh.bayry@crc.jussieu.fr.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>01</Month><Day>23</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Cell Death Dis</MedlineTA><NlmUniqueID>101524092</NlmUniqueID></MedlineJournalInfo><CitationSubset>IM</CitationSubset></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>09</Month><Day>26</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>01</Month><Day>09</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2020</Year><Month>01</Month><Day>08</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>1</Month><Day>25</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>1</Month><Day>25</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>1</Month><Day>25</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31974400</ArticleId><ArticleId IdType="doi">10.1038/s41419-020-2249-y</ArticleId><ArticleId IdType="pii">10.1038/s41419-020-2249-y</ArticleId><ArticleId 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first="Srini V" last="Kaveri">Srini V. Kaveri</name><name sortKey="Kaveri, Srini V" sort="Kaveri, Srini V" uniqKey="Kaveri S" first="Srini V" last="Kaveri">Srini V. Kaveri</name><name sortKey="Kumar Sharma, Varun" sort="Kumar Sharma, Varun" uniqKey="Kumar Sharma V" first="Varun" last="Kumar Sharma">Varun Kumar Sharma</name><name sortKey="Lecerf, Maxime" sort="Lecerf, Maxime" uniqKey="Lecerf M" first="Maxime" last="Lecerf">Maxime Lecerf</name><name sortKey="Lecerf, Maxime" sort="Lecerf, Maxime" uniqKey="Lecerf M" first="Maxime" last="Lecerf">Maxime Lecerf</name><name sortKey="Patil, Veerupaxagouda" sort="Patil, Veerupaxagouda" uniqKey="Patil V" first="Veerupaxagouda" last="Patil">Veerupaxagouda Patil</name><name sortKey="Rambabu, Naresh" sort="Rambabu, Naresh" uniqKey="Rambabu N" first="Naresh" last="Rambabu">Naresh Rambabu</name><name sortKey="Stephen Victor, Emmanuel" sort="Stephen Victor, Emmanuel" uniqKey="Stephen Victor E" first="Emmanuel" last="Stephen-Victor">Emmanuel Stephen-Victor</name></country><country name="Inde"><noRegion><name sortKey="Bhatt, Bharat" sort="Bhatt, Bharat" uniqKey="Bhatt B" first="Bharat" last="Bhatt">Bharat Bhatt</name></noRegion><name sortKey="Narayanaswamy Balaji, Kithiganahalli" sort="Narayanaswamy Balaji, Kithiganahalli" uniqKey="Narayanaswamy Balaji K" first="Kithiganahalli" last="Narayanaswamy Balaji">Kithiganahalli Narayanaswamy Balaji</name></country><country name="Suisse"><region name="Canton de Berne"><name sortKey="K Sermann, Fabian" sort="K Sermann, Fabian" uniqKey="K Sermann F" first="Fabian" last="K Sermann">Fabian K Sermann</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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