1. Pathogenic Role for γδ T Cells in Autoimmune Anti-Myeloperoxidase Glomerulonephritis.
- Author
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Poh-Yi Gan, Takeshi Fujita, Ooi, Joshua Daniel, Alikhan, Maliha Asghar, Dick, Jonathan, Shim, Raymond, Odobasic, Dragana, O'Sullivan, Kim Maree, Kitching, Arthur Richard, and Holdsworth, Stephen Roger
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MYELOPEROXIDASE , *CYTOPLASMIC filaments , *AUTOIMMUNITY , *T cells , *GLOMERULONEPHRITIS - Abstract
Myeloperoxidase (MPO) anti-neutrophil cytoplasmic Ab (ANCA)--associated vasculitis results from autoimmunity to MPO. IL-17A plays a critical role in generating this form of autoimmune injury but its cell of origin is uncertain. We addressed the hypothesis that IL-17A--producing γδ T cells are a nonredundant requisite in the development of MPO autoimmunity and glomerulonephritis (GN).We studied MPO-ANCA GN in wild type, αβ, or γδ T cell--deficient (C57BL/6, βTCR-/-, and δTCR-/- respectively) mice. Both T cell populations played important roles in the generation of autoimmunity to MPO and GN. Humoral autoimmunity was dependent on intact αβ T cells but was unaffected by γδ T cell deletion. Following MPO immunization, activated γδ T cells migrate to draining lymph nodes. Studies in dTCR-/- and transfer of γδ T cells to δTCR-/- mice show that γδ T cells facilitate the generation of anti-MPO autoimmunity and GN. dTCR-/- mice that received IL-17A-/- γδ T cells demonstrate that the development of anti-MPO autoimmunity and GN are dependent on γδ T cell IL-17A production. Finally, transfer of anti-MPO CD4+ T cell clones to naive δTCR-/- and wild type mice with planted glomerular MPO shows that γδ T cells are also necessary for recruitment of anti-MPO αβ CD4+ effector T cells. This study demonstrates that IL-17A produced by γδ T cells plays a critical role in the pathogenesis of MPO-ANCA GN by promoting the development of MPO-specific αβ T cells. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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