Interleukin-33 Contributes Toward Loss of Tolerance by Promoting B-Cell-Activating Factor of the Tumor-Necrosis-Factor Family (BAFF)-Dependent Autoantibody Production
| Autor: | Ningjie N. Hu, William A. Rose, Yi Ting Koh, Kristine Kay Kikly, Angela J. Okragly, Montanea R. Daniels, Andrea P. Martin, Robert J. Benschop |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
lcsh:Immunologic diseases. Allergy immune tolerance Neutrophils autoantibodies Primary Cell Culture Immunology medicine.disease_cause Autoantigens Autoimmune Diseases Immune tolerance Autoimmunity Mice 03 medical and health sciences 0302 clinical medicine B-Cell Activating Factor medicine Animals Humans Immunology and Allergy B-cell activating factor Cells Cultured B cell Original Research Mice Knockout B-Lymphocytes Chemistry Autoantibody Germinal center Dendritic Cells Interleukin-33 Recombinant Proteins Mice Inbred C57BL Interleukin 33 Disease Models Animal 030104 developmental biology medicine.anatomical_structure Immunoglobulin M germinal center radiation resistant IL-33 BAFF Tumor necrosis factor alpha lcsh:RC581-607 030215 immunology |
| Zdroj: | Frontiers in Immunology, Vol 9 (2018) Frontiers in Immunology |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2018.02871/full |
| Popis: | Breaking tolerance is a key event leading to autoimmunity, but the exact mechanisms responsible for this remain uncertain. Here we show that the alarmin IL-33 is able to drive the generation of autoantibodies through induction of the B cell survival factor BAFF. A temporary, short-term increase in IL-33 results in a primary (IgM) response to self-antigens. This transient DNA-specific autoantibody response was dependent on the induction of BAFF. Notably, radiation resistant cells and not myeloid cells, such as neutrophils or dendritic cells were the major source of BAFF and were critical in driving the autoantibody response. Chronic exposure to IL-33 elicited dramatic increases in BAFF levels and resulted in elevated numbers of B and T follicular helper cells as well as germinal center formation. We also observed class-switching from an IgM to an IgG DNA-specific autoantibody response. Collectively, the results provide novel insights into a potential mechanism for breaking immune-tolerance via IL-33-mediated induction of BAFF. |
| Databáze: | OpenAIRE |
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