PI3K pathway defects leading to immunodeficiency and immune dysregulation.
Identifieur interne : 000264 ( Main/Exploration ); précédent : 000263; suivant : 000265PI3K pathway defects leading to immunodeficiency and immune dysregulation.
Auteurs : Cristiane J. Nunes-Santos [Brésil] ; Gulbu Uzel ; Sergio D. RosenzweigSource :
- The Journal of allergy and clinical immunology [ 1097-6825 ] ; 2019.
Descripteurs français
- KwdFr :
- Animaux (MeSH), Auto-immunité (MeSH), Différenciation cellulaire (MeSH), Déficits immunitaires (génétique), Déficits immunitaires (métabolisme), Humains (MeSH), Immunité humorale (MeSH), Mutation (génétique), Phosphatidylinositol 3-kinases (métabolisme), Phosphatidylinositol 3-kinases de classe I (génétique), Phosphatidylinositol 3-kinases de classe I (métabolisme), Phénotype (MeSH), Système immunitaire (physiologie), Transduction du signal (MeSH).
- MESH :
- génétique : Déficits immunitaires, Mutation, Phosphatidylinositol 3-kinases de classe I.
- métabolisme : Déficits immunitaires, Phosphatidylinositol 3-kinases, Phosphatidylinositol 3-kinases de classe I.
- physiologie : Système immunitaire.
- Animaux, Auto-immunité, Différenciation cellulaire, Humains, Immunité humorale, Phénotype, Transduction du signal.
English descriptors
- KwdEn :
- Animals (MeSH), Autoimmunity (MeSH), Cell Differentiation (MeSH), Class I Phosphatidylinositol 3-Kinases (genetics), Class I Phosphatidylinositol 3-Kinases (metabolism), Humans (MeSH), Immune System (physiology), Immunity, Humoral (MeSH), Immunologic Deficiency Syndromes (genetics), Immunologic Deficiency Syndromes (metabolism), Mutation (genetics), Phenotype (MeSH), Phosphatidylinositol 3-Kinases (metabolism), Signal Transduction (MeSH).
- MESH :
- chemical , genetics : Class I Phosphatidylinositol 3-Kinases.
- chemical , metabolism : Class I Phosphatidylinositol 3-Kinases.
- genetics : Immunologic Deficiency Syndromes, Mutation.
- metabolism : Immunologic Deficiency Syndromes, Phosphatidylinositol 3-Kinases.
- physiology : Immune System.
- Animals, Autoimmunity, Cell Differentiation, Humans, Immunity, Humoral, Phenotype, Signal Transduction.
Abstract
The phosphatidylinositol 3-kinase (PI3K) signaling pathway is involved in a broad range of cellular processes, including growth, metabolism, differentiation, proliferation, motility, and survival. The PI3Kδ enzyme complex is primarily present in the immune system and comprises a catalytic (p110δ) and regulatory (p85α) subunit. Dynamic regulation of PI3Kδ activity is required to ensure normal function and differentiation of immune cells. In the last decade, discovery of germline mutations in genes involved in the PI3Kδ pathway (PIK3CD, PIK3R1, or phosphatase and tensin homolog [PTEN]) proved that both overactivation and underactivation (gain of function and loss of function, respectively) of PI3Kδ lead to impaired and dysregulated immunity. Although a small group of patients reported to underactivate PI3Kδ show predominantly humoral defects and autoimmune features, more than 200 patients have been described with overactivation of PI3Kδ, presenting with a much more complex phenotype of combined immunodeficiency and immune dysregulation. The clinical and immunologic characterization, as well as current pathophysiologic understanding and specific therapies for PI3K pathway defects leading to immunodeficiency and immune dysregulation, are reviewed here.
DOI: 10.1016/j.jaci.2019.03.017
PubMed: 31060715
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
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Electronic address: srosenzweig@cc.nih.gov.</nlm:affiliation><wicri:noCountry code="subField">Md</wicri:noCountry></affiliation></author></analytic><series><title level="j">The Journal of allergy and clinical immunology</title><idno type="eISSN">1097-6825</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term><term>Autoimmunity (MeSH)</term><term>Cell Differentiation (MeSH)</term><term>Class I Phosphatidylinositol 3-Kinases (genetics)</term><term>Class I Phosphatidylinositol 3-Kinases (metabolism)</term><term>Humans (MeSH)</term><term>Immune System (physiology)</term><term>Immunity, Humoral (MeSH)</term><term>Immunologic Deficiency Syndromes (genetics)</term><term>Immunologic Deficiency Syndromes (metabolism)</term><term>Mutation (genetics)</term><term>Phenotype (MeSH)</term><term>Phosphatidylinositol 3-Kinases (metabolism)</term><term>Signal Transduction (MeSH)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux (MeSH)</term><term>Auto-immunité (MeSH)</term><term>Différenciation cellulaire (MeSH)</term><term>Déficits immunitaires (génétique)</term><term>Déficits immunitaires (métabolisme)</term><term>Humains (MeSH)</term><term>Immunité humorale (MeSH)</term><term>Mutation (génétique)</term><term>Phosphatidylinositol 3-kinases (métabolisme)</term><term>Phosphatidylinositol 3-kinases de classe I (génétique)</term><term>Phosphatidylinositol 3-kinases de classe I (métabolisme)</term><term>Phénotype (MeSH)</term><term>Système immunitaire (physiologie)</term><term>Transduction du signal (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Class I Phosphatidylinositol 3-Kinases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Class I Phosphatidylinositol 3-Kinases</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Immunologic Deficiency Syndromes</term><term>Mutation</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Déficits immunitaires</term><term>Mutation</term><term>Phosphatidylinositol 3-kinases de classe I</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Immunologic Deficiency Syndromes</term><term>Phosphatidylinositol 3-Kinases</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Déficits immunitaires</term><term>Phosphatidylinositol 3-kinases</term><term>Phosphatidylinositol 3-kinases de classe I</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Système immunitaire</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Immune System</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Autoimmunity</term><term>Cell Differentiation</term><term>Humans</term><term>Immunity, Humoral</term><term>Phenotype</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Auto-immunité</term><term>Différenciation cellulaire</term><term>Humains</term><term>Immunité humorale</term><term>Phénotype</term><term>Transduction du signal</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The phosphatidylinositol 3-kinase (PI3K) signaling pathway is involved in a broad range of cellular processes, including growth, metabolism, differentiation, proliferation, motility, and survival. The PI3Kδ enzyme complex is primarily present in the immune system and comprises a catalytic (p110δ) and regulatory (p85α) subunit. Dynamic regulation of PI3Kδ activity is required to ensure normal function and differentiation of immune cells. In the last decade, discovery of germline mutations in genes involved in the PI3Kδ pathway (PIK3CD, PIK3R1, or phosphatase and tensin homolog [PTEN]) proved that both overactivation and underactivation (gain of function and loss of function, respectively) of PI3Kδ lead to impaired and dysregulated immunity. Although a small group of patients reported to underactivate PI3Kδ show predominantly humoral defects and autoimmune features, more than 200 patients have been described with overactivation of PI3Kδ, presenting with a much more complex phenotype of combined immunodeficiency and immune dysregulation. The clinical and immunologic characterization, as well as current pathophysiologic understanding and specific therapies for PI3K pathway defects leading to immunodeficiency and immune dysregulation, are reviewed here.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">31060715</PMID><DateCompleted><Year>2020</Year><Month>06</Month><Day>08</Day></DateCompleted><DateRevised><Year>2020</Year><Month>06</Month><Day>08</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1097-6825</ISSN><JournalIssue CitedMedium="Internet"><Volume>143</Volume><Issue>5</Issue><PubDate><Year>2019</Year><Month>05</Month></PubDate></JournalIssue><Title>The Journal of allergy and clinical immunology</Title><ISOAbbreviation>J Allergy Clin Immunol</ISOAbbreviation></Journal><ArticleTitle>PI3K pathway defects leading to immunodeficiency and immune dysregulation.</ArticleTitle><Pagination><MedlinePgn>1676-1687</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S0091-6749(19)30421-X</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.jaci.2019.03.017</ELocationID><Abstract><AbstractText>The phosphatidylinositol 3-kinase (PI3K) signaling pathway is involved in a broad range of cellular processes, including growth, metabolism, differentiation, proliferation, motility, and survival. The PI3Kδ enzyme complex is primarily present in the immune system and comprises a catalytic (p110δ) and regulatory (p85α) subunit. Dynamic regulation of PI3Kδ activity is required to ensure normal function and differentiation of immune cells. In the last decade, discovery of germline mutations in genes involved in the PI3Kδ pathway (PIK3CD, PIK3R1, or phosphatase and tensin homolog [PTEN]) proved that both overactivation and underactivation (gain of function and loss of function, respectively) of PI3Kδ lead to impaired and dysregulated immunity. Although a small group of patients reported to underactivate PI3Kδ show predominantly humoral defects and autoimmune features, more than 200 patients have been described with overactivation of PI3Kδ, presenting with a much more complex phenotype of combined immunodeficiency and immune dysregulation. The clinical and immunologic characterization, as well as current pathophysiologic understanding and specific therapies for PI3K pathway defects leading to immunodeficiency and immune dysregulation, are reviewed here.</AbstractText><CopyrightInformation>Published by Elsevier Inc.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Nunes-Santos</LastName><ForeName>Cristiane J</ForeName><Initials>CJ</Initials><AffiliationInfo><Affiliation>Immunology Service, Department of Laboratory Medicine, National Institutes of Health (NIH) Clinical Center, Bethesda, Md; Faculdade de Medicina, Instituto da Crianca, Universidade de São Paulo, São Paulo, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Uzel</LastName><ForeName>Gulbu</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Md.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rosenzweig</LastName><ForeName>Sergio D</ForeName><Initials>SD</Initials><AffiliationInfo><Affiliation>Immunology Service, Department of Laboratory Medicine, National Institutes of Health (NIH) Clinical Center, Bethesda, Md. 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Rosenzweig</name><name sortKey="Uzel, Gulbu" sort="Uzel, Gulbu" uniqKey="Uzel G" first="Gulbu" last="Uzel">Gulbu Uzel</name></noCountry><country name="Brésil"><region name="État de São Paulo"><name sortKey="Nunes Santos, Cristiane J" sort="Nunes Santos, Cristiane J" uniqKey="Nunes Santos C" first="Cristiane J" last="Nunes-Santos">Cristiane J. Nunes-Santos</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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