CD11c-mediated deletion of Flip promotes autoreactivity and inflammatory arthritis
| Autor: | Zan Huang, Qi Quan Huang, Renee Doyle, Deyu Fang, Syamal K. Datta, Quan Zhen Li, Hyewon Phee, Robert Birkett, Harris Perlman, Richard M. Pope, William H. Robinson, G. Kenneth Haines |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male Inflammatory arthritis CASP8 and FADD-Like Apoptosis Regulating Protein General Physics and Astronomy Arthritis CD11c chemical and pharmacologic phenomena T-Lymphocytes Regulatory Article General Biochemistry Genetics and Molecular Biology Autoimmune Diseases Pathogenesis Mice 03 medical and health sciences 0302 clinical medicine Immune system medicine Animals Autoantibodies 030304 developmental biology Inflammation Mice Knockout 0303 health sciences Multidisciplinary business.industry Autoantibody hemic and immune systems Dendritic Cells General Chemistry medicine.disease CD11c Antigen 3. Good health Flip Rheumatoid arthritis Immunology Female business 030215 immunology |
| Zdroj: | Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Dendritic cells (DCs) are critical for immune homeostasis. To target DCs, we generated a mouse line with Flip deficiency in cells that express cre under the CD11c promoter (CD11c-Flip-KO). CD11c-Flip-KO mice spontaneously develop erosive, inflammatory arthritis, resembling rheumatoid arthritis, which is dramatically reduced when these mice are crossed with Rag−/− mice. The CD8α+ DC subset is significantly reduced, along with alterations in NK cells and macrophages. Autoreactive CD4+ T cells and autoantibodies specific for joint tissue are present, and arthritis severity correlates with the number of autoreactive CD4+ T cells and plasmablasts in the joint-draining lymph nodes. Reduced T regulatory cells (Tregs) inversely correlate with arthritis severity, and the transfer of Tregs ameliorates arthritis. This KO line identifies a model that will permit in depth interrogation of the pathogenesis of rheumatoid arthritis, including the role of CD8α+ DCs and other cells of the immune system. Dendritic cells are critical for initiation of immune responses and for induction of tolerance. Here the authors show that deletion of survival factor c-flip in CD11c-expressing cells subset perturbs CD8a+ dendritic cell, NK and macrophage pools, and leads to development of autoimmune arthritis. |
| Databáze: | OpenAIRE |
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