| First Author | Gan PY | Year | 2017 |
| Journal | J Immunol | Volume | 199 |
| Issue | 9 | Pages | 3042-3050 |
| PubMed ID | 28954887 | Mgi Jnum | J:254743 |
| Mgi Id | MGI:6103718 | Doi | 10.4049/jimmunol.1602025 |
| Citation | Gan PY, et al. (2017) Pathogenic Role for gammadelta T Cells in Autoimmune Anti-Myeloperoxidase Glomerulonephritis. J Immunol 199(9):3042-3050 |
| abstractText | 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 gammadelta T cells are a nonredundant requisite in the development of MPO autoimmunity and glomerulonephritis (GN). We studied MPO-ANCA GN in wild type, alphabeta, or gammadelta T cell-deficient (C57BL/6, betaTCR(-/-) , and deltaTCR(-/-) respectively) mice. Both T cell populations played important roles in the generation of autoimmunity to MPO and GN. Humoral autoimmunity was dependent on intact alphabeta T cells but was unaffected by gammadelta T cell deletion. Following MPO immunization, activated gammadelta T cells migrate to draining lymph nodes. Studies in deltaTCR(-/-) and transfer of gammadelta T cells to deltaTCR(-/-) mice show that gammadelta T cells facilitate the generation of anti-MPO autoimmunity and GN. deltaTCR(-/-) mice that received IL-17A(-/-) gammadelta T cells demonstrate that the development of anti-MPO autoimmunity and GN are dependent on gammadelta T cell IL-17A production. Finally, transfer of anti-MPO CD4(+) T cell clones to naive deltaTCR(-/-) and wild type mice with planted glomerular MPO shows that gammadelta T cells are also necessary for recruitment of anti-MPO alphabeta CD4(+) effector T cells. This study demonstrates that IL-17A produced by gammadelta T cells plays a critical role in the pathogenesis of MPO-ANCA GN by promoting the development of MPO-specific alphabeta T cells. |
