Polarization of Rheumatoid Macrophages by TNF Targeting Through an IL-10/STAT3 Mechanism
Identifieur interne : 000076 ( France/Analysis ); précédent : 000075; suivant : 000077Polarization of Rheumatoid Macrophages by TNF Targeting Through an IL-10/STAT3 Mechanism
Auteurs : Yannick Degboé [France] ; Benjamin Rauwel [France] ; Michel Baron [France] ; Jean-Frédéric Boyer [France] ; Adeline Ruyssen-Witrand [France] ; Arnaud Constantin [France] ; Jean-Luc Davignon [France]Source :
- Frontiers in Immunology [ 1664-3224 ] ; 2019.
Descripteurs français
- KwdFr :
- Activation des macrophages (immunologie), Adulte d'âge moyen, Agranulocytes (), Agranulocytes (immunologie), Agranulocytes (métabolisme), Analyse de profil d'expression de gènes, Cellules cultivées, Cytokines (métabolisme), Facteur de nécrose tumorale alpha (antagonistes et inhibiteurs), Facteur de nécrose tumorale alpha (métabolisme), Facteur de transcription STAT-3 (métabolisme), Femelle, Humains, Immunophénotypage, Interleukine-10 (métabolisme), Macrophages (), Macrophages (immunologie), Macrophages (métabolisme), Marqueurs biologiques, Mâle, Polyarthrite rhumatoïde (), Polyarthrite rhumatoïde (diagnostic), Polyarthrite rhumatoïde (immunologie), Polyarthrite rhumatoïde (métabolisme), Sujet âgé.
- MESH :
- antagonistes et inhibiteurs : Facteur de nécrose tumorale alpha.
- diagnostic : Polyarthrite rhumatoïde.
- immunologie : Activation des macrophages, Agranulocytes, Macrophages, Polyarthrite rhumatoïde.
- métabolisme : Agranulocytes, Cytokines, Facteur de nécrose tumorale alpha, Facteur de transcription STAT-3, Interleukine-10, Macrophages, Polyarthrite rhumatoïde.
- Adulte d'âge moyen, Agranulocytes, Analyse de profil d'expression de gènes, Cellules cultivées, Femelle, Humains, Immunophénotypage, Macrophages, Marqueurs biologiques, Mâle, Polyarthrite rhumatoïde, Sujet âgé.
English descriptors
- KwdEn :
- Aged, Arthritis, Rheumatoid (diagnosis), Arthritis, Rheumatoid (immunology), Arthritis, Rheumatoid (metabolism), Arthritis, Rheumatoid (therapy), Biomarkers, Cells, Cultured, Cytokines (metabolism), Female, Gene Expression Profiling, Humans, Immunophenotyping, Interleukin-10 (metabolism), Leukocytes, Mononuclear (drug effects), Leukocytes, Mononuclear (immunology), Leukocytes, Mononuclear (metabolism), Macrophage Activation (immunology), Macrophages (drug effects), Macrophages (immunology), Macrophages (metabolism), Male, Middle Aged, STAT3 Transcription Factor (metabolism), Tumor Necrosis Factor-alpha (antagonists & inhibitors), Tumor Necrosis Factor-alpha (metabolism).
- MESH :
- chemical , antagonists & inhibitors : Tumor Necrosis Factor-alpha.
- chemical , metabolism : Cytokines, Interleukin-10, STAT3 Transcription Factor, Tumor Necrosis Factor-alpha.
- chemical : Biomarkers.
- diagnosis : Arthritis, Rheumatoid.
- drug effects : Leukocytes, Mononuclear, Macrophages.
- immunology : Arthritis, Rheumatoid, Leukocytes, Mononuclear, Macrophage Activation, Macrophages.
- metabolism : Arthritis, Rheumatoid, Leukocytes, Mononuclear, Macrophages.
- therapy : Arthritis, Rheumatoid.
- Aged, Cells, Cultured, Female, Gene Expression Profiling, Humans, Immunophenotyping, Male, Middle Aged.
Abstract
Macrophages contribute to the pathogenesis of rheumatoid arthritis (RA). They can display different states of activation or “polarization,” notably the so-called inflammatory “M1” and the various alternative “M2” polarizations, characterized by distinct functions. Data regarding the effects of RA anti-cytokine biological disease-modifying anti-rheumatic drugs (bDMARDs) on macrophage polarization are scarce. We aimed to assess
Url:
DOI: 10.3389/fimmu.2019.00003
PubMed: 30713533
PubMed Central: 6345709
Affiliations:
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uniqKey="Degboe Y" first="Yannick" last="Degboé">Yannick Degboé</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Centre de Physiopathologie Toulouse Purpan, INSERM UMR 1043</institution>,<addr-line>Toulouse</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Centre de Rhumatologie, CHU de Toulouse</institution>,<addr-line>Toulouse</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Faculté de Médecine, Université Paul Sabatier Toulouse III</institution>,<addr-line>Toulouse</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Rauwel, Benjamin" sort="Rauwel, Benjamin" uniqKey="Rauwel B" first="Benjamin" last="Rauwel">Benjamin Rauwel</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Centre de Physiopathologie Toulouse Purpan, INSERM UMR 1043</institution>,<addr-line>Toulouse</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Baron, Michel" sort="Baron, Michel" uniqKey="Baron M" first="Michel" last="Baron">Michel Baron</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Centre de Physiopathologie Toulouse Purpan, INSERM UMR 1043</institution>,<addr-line>Toulouse</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Boyer, Jean Frederic" sort="Boyer, Jean Frederic" uniqKey="Boyer J" first="Jean-Frédéric" last="Boyer">Jean-Frédéric Boyer</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Centre de Physiopathologie Toulouse Purpan, INSERM UMR 1043</institution>,<addr-line>Toulouse</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Centre de Rhumatologie, CHU de Toulouse</institution>,<addr-line>Toulouse</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ruyssen Witrand, Adeline" sort="Ruyssen Witrand, Adeline" uniqKey="Ruyssen Witrand A" first="Adeline" last="Ruyssen-Witrand">Adeline Ruyssen-Witrand</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Centre de Rhumatologie, CHU de Toulouse</institution>,<addr-line>Toulouse</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Faculté de Médecine, Université Paul Sabatier Toulouse III</institution>,<addr-line>Toulouse</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>UMR1027, INSERM—Université Paul Sabatier Toulouse III</institution>,<addr-line>Toulouse</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Constantin, Arnaud" sort="Constantin, Arnaud" uniqKey="Constantin A" first="Arnaud" last="Constantin">Arnaud Constantin</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Centre de Physiopathologie Toulouse Purpan, INSERM UMR 1043</institution>,<addr-line>Toulouse</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Centre de Rhumatologie, CHU de Toulouse</institution>,<addr-line>Toulouse</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Faculté de Médecine, Université Paul Sabatier Toulouse III</institution>,<addr-line>Toulouse</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Davignon, Jean Luc" sort="Davignon, Jean Luc" uniqKey="Davignon J" first="Jean-Luc" last="Davignon">Jean-Luc Davignon</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Centre de Physiopathologie Toulouse Purpan, INSERM UMR 1043</institution>,<addr-line>Toulouse</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Centre de Rhumatologie, CHU de Toulouse</institution>,<addr-line>Toulouse</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Frontiers in Immunology</title><idno type="eISSN">1664-3224</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Arthritis, Rheumatoid (diagnosis)</term><term>Arthritis, Rheumatoid (immunology)</term><term>Arthritis, Rheumatoid (metabolism)</term><term>Arthritis, Rheumatoid (therapy)</term><term>Biomarkers</term><term>Cells, Cultured</term><term>Cytokines (metabolism)</term><term>Female</term><term>Gene Expression Profiling</term><term>Humans</term><term>Immunophenotyping</term><term>Interleukin-10 (metabolism)</term><term>Leukocytes, Mononuclear (drug effects)</term><term>Leukocytes, Mononuclear (immunology)</term><term>Leukocytes, Mononuclear (metabolism)</term><term>Macrophage Activation (immunology)</term><term>Macrophages (drug effects)</term><term>Macrophages (immunology)</term><term>Macrophages (metabolism)</term><term>Male</term><term>Middle Aged</term><term>STAT3 Transcription Factor (metabolism)</term><term>Tumor Necrosis Factor-alpha (antagonists & inhibitors)</term><term>Tumor Necrosis Factor-alpha (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Activation des macrophages (immunologie)</term><term>Adulte d'âge moyen</term><term>Agranulocytes ()</term><term>Agranulocytes (immunologie)</term><term>Agranulocytes (métabolisme)</term><term>Analyse de profil d'expression de gènes</term><term>Cellules cultivées</term><term>Cytokines (métabolisme)</term><term>Facteur de nécrose tumorale alpha (antagonistes et inhibiteurs)</term><term>Facteur de nécrose tumorale alpha (métabolisme)</term><term>Facteur de transcription STAT-3 (métabolisme)</term><term>Femelle</term><term>Humains</term><term>Immunophénotypage</term><term>Interleukine-10 (métabolisme)</term><term>Macrophages ()</term><term>Macrophages (immunologie)</term><term>Macrophages (métabolisme)</term><term>Marqueurs biologiques</term><term>Mâle</term><term>Polyarthrite rhumatoïde ()</term><term>Polyarthrite rhumatoïde (diagnostic)</term><term>Polyarthrite rhumatoïde (immunologie)</term><term>Polyarthrite rhumatoïde (métabolisme)</term><term>Sujet âgé</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Tumor Necrosis Factor-alpha</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cytokines</term><term>Interleukin-10</term><term>STAT3 Transcription Factor</term><term>Tumor Necrosis Factor-alpha</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Biomarkers</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Facteur de nécrose tumorale alpha</term></keywords><keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Arthritis, Rheumatoid</term></keywords><keywords scheme="MESH" qualifier="diagnostic" xml:lang="fr"><term>Polyarthrite rhumatoïde</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Leukocytes, Mononuclear</term><term>Macrophages</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Activation des macrophages</term><term>Agranulocytes</term><term>Macrophages</term><term>Polyarthrite rhumatoïde</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Arthritis, Rheumatoid</term><term>Leukocytes, Mononuclear</term><term>Macrophage Activation</term><term>Macrophages</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Arthritis, Rheumatoid</term><term>Leukocytes, Mononuclear</term><term>Macrophages</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Agranulocytes</term><term>Cytokines</term><term>Facteur de nécrose tumorale alpha</term><term>Facteur de transcription STAT-3</term><term>Interleukine-10</term><term>Macrophages</term><term>Polyarthrite rhumatoïde</term></keywords><keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Arthritis, Rheumatoid</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Cells, Cultured</term><term>Female</term><term>Gene Expression Profiling</term><term>Humans</term><term>Immunophenotyping</term><term>Male</term><term>Middle Aged</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte d'âge moyen</term><term>Agranulocytes</term><term>Analyse de profil d'expression de gènes</term><term>Cellules cultivées</term><term>Femelle</term><term>Humains</term><term>Immunophénotypage</term><term>Macrophages</term><term>Marqueurs biologiques</term><term>Mâle</term><term>Polyarthrite rhumatoïde</term><term>Sujet âgé</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Macrophages contribute to the pathogenesis of rheumatoid arthritis (RA). They can display different states of activation or “polarization,” notably the so-called inflammatory “M1” and the various alternative “M2” polarizations, characterized by distinct functions. Data regarding the effects of RA anti-cytokine biological disease-modifying anti-rheumatic drugs (bDMARDs) on macrophage polarization are scarce. We aimed to assess <italic>in vitro</italic> modulation of macrophage polarization by bDMARDs targeting pro-inflammatory cytokines in RA. We generated monocyte derived macrophages using blood samples from 20 RA patients with active RA and 30 healthy controls. We evaluated <italic>in vitro</italic> the impact on M1 inflammatory macrophages of: etanercept (ETA), adalimumab (ADA), certolizumab (CZP), tocilizumab (TCZ), and rituximab (RTX). We assessed the impact on macrophage polarization using flow cytometry and RTqPCR to study the expression of surface markers and perform functional studies of cytokine production, phagocytosis, and negative feedback control of inflammation. Among evaluated bDMARDs, anti-TNF agents modulated the polarization of inflammatory macrophages by decreasing inflammatory surface markers (CD40, CD80) and favoring alternative markers (CD16, CD163, MerTK). Anti-TNF agents also induced alternative functions in macrophages activated in inflammatory condition with (i) the inhibition of inflammatory cytokines (TNF, IL-6, IL-12), (ii) an increase in phagocytosis. These findings were mechanistically related to an increase in early IL-10 production, responsible for higher negative feedback control of inflammation involving SOCS3 and Gas6. This IL-10 effect was STAT3-dependent. Anti-TNF agents not only inhibit <italic>in vitro</italic> inflammatory functions of macrophages, but also favor resolution of inflammation through polarization toward alternative features specifically involving the IL-10/STAT3 axis.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Gordon, S" uniqKey="Gordon S">S Gordon</name></author><author><name sortKey="Martinez, Fo" uniqKey="Martinez F">FO Martinez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Martinez, Fo" uniqKey="Martinez F">FO Martinez</name></author><author><name sortKey="Gordon, S" uniqKey="Gordon S">S Gordon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xue, J" uniqKey="Xue J">J Xue</name></author><author><name sortKey="Schmidt, Sv" uniqKey="Schmidt S">SV Schmidt</name></author><author><name sortKey="Sander, J" uniqKey="Sander J">J Sander</name></author><author><name sortKey="Draffehn, A" 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P" uniqKey="Miossec P">P Miossec</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Roberts, Ca" uniqKey="Roberts C">CA Roberts</name></author><author><name sortKey="Durham, Le" uniqKey="Durham L">LE Durham</name></author><author><name sortKey="Fleskens, V" uniqKey="Fleskens V">V Fleskens</name></author><author><name sortKey="Evans, Hg" uniqKey="Evans H">HG Evans</name></author><author><name sortKey="Taams, Ls" uniqKey="Taams L">LS Taams</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alciato, F" uniqKey="Alciato F">F Alciato</name></author><author><name sortKey="Sainaghi, Pp" uniqKey="Sainaghi P">PP Sainaghi</name></author><author><name sortKey="Sola, D" uniqKey="Sola D">D Sola</name></author><author><name sortKey="Castello, L" uniqKey="Castello L">L Castello</name></author><author><name sortKey="Avanzi, Gc" uniqKey="Avanzi G">GC Avanzi</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>France</li></country></list><tree><country name="France"><noRegion><name sortKey="Degboe, Yannick" sort="Degboe, Yannick" uniqKey="Degboe Y" first="Yannick" last="Degboé">Yannick Degboé</name></noRegion><name sortKey="Baron, Michel" sort="Baron, Michel" uniqKey="Baron M" first="Michel" last="Baron">Michel Baron</name><name sortKey="Boyer, Jean Frederic" sort="Boyer, Jean Frederic" uniqKey="Boyer J" first="Jean-Frédéric" last="Boyer">Jean-Frédéric Boyer</name><name sortKey="Boyer, Jean Frederic" sort="Boyer, Jean Frederic" uniqKey="Boyer J" first="Jean-Frédéric" last="Boyer">Jean-Frédéric Boyer</name><name sortKey="Constantin, Arnaud" sort="Constantin, Arnaud" uniqKey="Constantin A" first="Arnaud" last="Constantin">Arnaud Constantin</name><name sortKey="Constantin, Arnaud" sort="Constantin, Arnaud" uniqKey="Constantin A" first="Arnaud" last="Constantin">Arnaud Constantin</name><name sortKey="Constantin, Arnaud" sort="Constantin, Arnaud" uniqKey="Constantin A" first="Arnaud" last="Constantin">Arnaud Constantin</name><name sortKey="Davignon, Jean Luc" sort="Davignon, Jean Luc" uniqKey="Davignon J" first="Jean-Luc" last="Davignon">Jean-Luc Davignon</name><name sortKey="Davignon, Jean Luc" sort="Davignon, Jean Luc" uniqKey="Davignon J" first="Jean-Luc" last="Davignon">Jean-Luc Davignon</name><name sortKey="Degboe, Yannick" sort="Degboe, Yannick" uniqKey="Degboe Y" first="Yannick" last="Degboé">Yannick Degboé</name><name sortKey="Degboe, Yannick" sort="Degboe, Yannick" uniqKey="Degboe Y" first="Yannick" last="Degboé">Yannick Degboé</name><name sortKey="Rauwel, Benjamin" sort="Rauwel, Benjamin" uniqKey="Rauwel B" first="Benjamin" last="Rauwel">Benjamin Rauwel</name><name sortKey="Ruyssen Witrand, Adeline" sort="Ruyssen Witrand, Adeline" uniqKey="Ruyssen Witrand A" first="Adeline" last="Ruyssen-Witrand">Adeline Ruyssen-Witrand</name><name sortKey="Ruyssen Witrand, Adeline" sort="Ruyssen Witrand, Adeline" uniqKey="Ruyssen Witrand A" first="Adeline" last="Ruyssen-Witrand">Adeline Ruyssen-Witrand</name><name sortKey="Ruyssen Witrand, Adeline" sort="Ruyssen Witrand, Adeline" uniqKey="Ruyssen Witrand A" first="Adeline" last="Ruyssen-Witrand">Adeline Ruyssen-Witrand</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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