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Invariant NKT cells limit activation of autoreactive CD1d-positive B cells

Faulty activation of autoreactive B cells is a hallmark of autoimmune diseases like systemic lupus erythematosus (SLE). An important feature restricting activation of autoreactive B cells is efficient removal of apoptotic material. Mounting evidence also connects a primary defect in invariant natura...

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Detalles Bibliográficos
Autores principales: Wermeling, Fredrik, Lind, Sara M., Jordö, Emilie Domange, Cardell, Susanna L., Karlsson, Mikael C.I.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867286/
https://www.ncbi.nlm.nih.gov/pubmed/20439539
http://dx.doi.org/10.1084/jem.20091314
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author Wermeling, Fredrik
Lind, Sara M.
Jordö, Emilie Domange
Cardell, Susanna L.
Karlsson, Mikael C.I.
author_facet Wermeling, Fredrik
Lind, Sara M.
Jordö, Emilie Domange
Cardell, Susanna L.
Karlsson, Mikael C.I.
author_sort Wermeling, Fredrik
collection PubMed
description Faulty activation of autoreactive B cells is a hallmark of autoimmune diseases like systemic lupus erythematosus (SLE). An important feature restricting activation of autoreactive B cells is efficient removal of apoptotic material. Mounting evidence also connects a primary defect in invariant natural killer T (iNKT) cells to autoimmune disease development. However, exactly how this unconventional T cell subset is involved remains to be defined. Here, we identify a suppressive role for iNKT cells in a model where autoantibody production is triggered by an increased load of circulating apoptotic cells, resembling the situation in SLE patients. Absence or reduction of iNKT cells as well as absence of CD1d-expression on B cells, needed for direct iNKT–B cell interaction, leads to increased autoreactive B cell activation and symptoms of disease. The suppression mediated by the iNKT cells is observed before B cell entry into germinal centers and can be rescued by transferring iNKT cells to deficient mice. This links iNKT cells to handling of dying cells and identifies a novel peripheral tolerance checkpoint relevant for autoimmune disease. Thus, these observations connect two clinical observations in SLE patients previously considered to be unrelated and define a new target for immunotherapy.
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spelling pubmed-28672862010-11-10 Invariant NKT cells limit activation of autoreactive CD1d-positive B cells Wermeling, Fredrik Lind, Sara M. Jordö, Emilie Domange Cardell, Susanna L. Karlsson, Mikael C.I. J Exp Med Brief Definitive Report Faulty activation of autoreactive B cells is a hallmark of autoimmune diseases like systemic lupus erythematosus (SLE). An important feature restricting activation of autoreactive B cells is efficient removal of apoptotic material. Mounting evidence also connects a primary defect in invariant natural killer T (iNKT) cells to autoimmune disease development. However, exactly how this unconventional T cell subset is involved remains to be defined. Here, we identify a suppressive role for iNKT cells in a model where autoantibody production is triggered by an increased load of circulating apoptotic cells, resembling the situation in SLE patients. Absence or reduction of iNKT cells as well as absence of CD1d-expression on B cells, needed for direct iNKT–B cell interaction, leads to increased autoreactive B cell activation and symptoms of disease. The suppression mediated by the iNKT cells is observed before B cell entry into germinal centers and can be rescued by transferring iNKT cells to deficient mice. This links iNKT cells to handling of dying cells and identifies a novel peripheral tolerance checkpoint relevant for autoimmune disease. Thus, these observations connect two clinical observations in SLE patients previously considered to be unrelated and define a new target for immunotherapy. The Rockefeller University Press 2010-05-10 /pmc/articles/PMC2867286/ /pubmed/20439539 http://dx.doi.org/10.1084/jem.20091314 Text en © 2010 Wermeling et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Brief Definitive Report
Wermeling, Fredrik
Lind, Sara M.
Jordö, Emilie Domange
Cardell, Susanna L.
Karlsson, Mikael C.I.
Invariant NKT cells limit activation of autoreactive CD1d-positive B cells
title Invariant NKT cells limit activation of autoreactive CD1d-positive B cells
title_full Invariant NKT cells limit activation of autoreactive CD1d-positive B cells
title_fullStr Invariant NKT cells limit activation of autoreactive CD1d-positive B cells
title_full_unstemmed Invariant NKT cells limit activation of autoreactive CD1d-positive B cells
title_short Invariant NKT cells limit activation of autoreactive CD1d-positive B cells
title_sort invariant nkt cells limit activation of autoreactive cd1d-positive b cells
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867286/
https://www.ncbi.nlm.nih.gov/pubmed/20439539
http://dx.doi.org/10.1084/jem.20091314
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