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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...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2010
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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. |
format | Text |
id | pubmed-2867286 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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