| Invariant NKT cells inhibit autoreactive B cells in a contact- and CD1d-dependent manner. | |
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MedLine Citation:
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PMID: 21209282 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Autoantibody production is a hallmark of autoimmune diseases, such as lupus and rheumatoid arthritis. Accumulating evidence suggests a role of invariant NKT (iNKT) cells in their pathogenesis. Mechanisms underlying the role of iNKT cells in these diseases, however, remain unclear. In this study, we show that iNKT cells suppress IgG anti-DNA Ab and rheumatoid factor production and reduce IL-10-secreting B cells in a contact-dependent manner, but increase total IgG production and enhance activation markers on B cells via soluble factors. In vivo reconstitution with iNKT cells also reduces autoantibody production in iNKT-deficient mice and in SCID mice implanted with B cells. Using an anti-DNA transgenic model, we found that autoreactive B cells spontaneously produce IL-10 and are activated in vivo. In the presence of activated iNKT cells, these autoreactive B cells are selectively reduced, whereas nonautoreactive B cells are markedly activated. Because iNKTs recognize CD1d, we reasoned that CD1d might play a role in the differential regulation of autoreactive versus nonautoreactive B cells by iNKT cells. Indeed, autoreactive B cells express more CD1d than nonautoreactive B cells, and CD1d deficiency in lupus mice exacerbates autoantibody production and enhances Ab response to a self-peptide but not to a foreign peptide. Importantly, iNKT cells fail to inhibit autoantibody production by CD1d-deficient B cells. Thus, iNKT cells inhibit autoreactive B cells in a contact- and CD1d-dependent manner but activate nonautoreactive B cells via cytokines. Such ability of iNKTs to suppress autoantibody production, without causing global suppression of B cells, has important implications for the development of iNKT-based therapy for autoimmune diseases. |
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Authors:
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Jun-Qi Yang; Xiangshu Wen; Peter J Kim; Ram Raj Singh |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-01-05 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 186 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-20 Completed Date: 2011-03-07 Revised Date: 2012-06-12 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 1512-20 Citation Subset: AIM; IM |
Affiliation:
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Autoimmunity and Tolerance Laboratory, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, CD1d / genetics, metabolism, physiology* Autoantibodies / biosynthesis, metabolism* B-Lymphocyte Subsets / immunology*, metabolism* Cell Adhesion / genetics, immunology* Galactosylceramides / pharmacology Immunoglobulin G / metabolism Immunosuppressive Agents / pharmacology Lymphocyte Activation / genetics, immunology Lymphocyte Depletion Mice Mice, Inbred BALB C Mice, Inbred NZB Mice, Knockout Mice, SCID Mice, Transgenic Natural Killer T-Cells / immunology*, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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AI80778/AI/NIAID NIH HHS; AR50797/AR/NIAMS NIH HHS; AR56465/AR/NIAMS NIH HHS; R01 AI080778/AI/NIAID NIH HHS; R01 AI080778-01A2/AI/NIAID NIH HHS; R01 AI080778-02/AI/NIAID NIH HHS; R01 AI080778-03/AI/NIAID NIH HHS; R01 AR050797-05/AR/NIAMS NIH HHS; R01 AR056465-02/AR/NIAMS NIH HHS; R01 AR056465-03/AR/NIAMS NIH HHS; R01 AR056465-04/AR/NIAMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD1d; 0/Autoantibodies; 0/Galactosylceramides; 0/Immunoglobulin G; 0/Immunosuppressive Agents; 0/alpha-galactosylceramide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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