TY - JOUR
T1 - Pathogenic role for γδ T cells in autoimmune anti-myeloperoxidase glomerulonephritis
AU - Gan, Poh Yi
AU - Fujita, Takeshi
AU - Ooi, Joshua Daniel
AU - Alikhan, Maliha Asghar
AU - Dick, Jonathan
AU - Shim, Raymond
AU - Odobasic, Dragana
AU - O'Sullivan, Kim Maree
AU - Kitching, Arthur Richard
AU - Holdsworth, Stephen Roger
PY - 2017/11/1
Y1 - 2017/11/1
N2 - 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 gd T cells are a nonredundant requisite in the development of MPO autoimmunity and glomerulonephritis (GN).We studied MPO-ANCA GN in wild type, ab, or gd T cell-deficient (C57BL/6, bTCR2/2, and dTCR2/2 respectively) mice. Both T cell populations played important roles in the generation of autoimmunity to MPO and GN. Humoral autoimmunity was dependent on intact ab T cells but was unaffected by gd T cell deletion. Following MPO immunization, activated gd T cells migrate to draining lymph nodes. Studies in dTCR2/2 and transfer of gd T cells to dTCR2/2 mice show that gd T cells facilitate the generation of anti-MPO autoimmunity and GN. dTCR2/2 mice that received IL-17A2/2 gd T cells demonstrate that the development of anti-MPO autoimmunity and GN are dependent on gd T cell IL-17A production. Finally, transfer of anti-MPO CD4+ T cell clones to naive dTCR2/2 and wild type mice with planted glomerular MPO shows that gd T cells are also necessary for recruitment of anti-MPO ab CD4+ effector T cells. This study demonstrates that IL-17A produced by gd T cells plays a critical role in the pathogenesis of MPO-ANCA GN by promoting the development of MPO-specific ab T cells.
AB - 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 gd T cells are a nonredundant requisite in the development of MPO autoimmunity and glomerulonephritis (GN).We studied MPO-ANCA GN in wild type, ab, or gd T cell-deficient (C57BL/6, bTCR2/2, and dTCR2/2 respectively) mice. Both T cell populations played important roles in the generation of autoimmunity to MPO and GN. Humoral autoimmunity was dependent on intact ab T cells but was unaffected by gd T cell deletion. Following MPO immunization, activated gd T cells migrate to draining lymph nodes. Studies in dTCR2/2 and transfer of gd T cells to dTCR2/2 mice show that gd T cells facilitate the generation of anti-MPO autoimmunity and GN. dTCR2/2 mice that received IL-17A2/2 gd T cells demonstrate that the development of anti-MPO autoimmunity and GN are dependent on gd T cell IL-17A production. Finally, transfer of anti-MPO CD4+ T cell clones to naive dTCR2/2 and wild type mice with planted glomerular MPO shows that gd T cells are also necessary for recruitment of anti-MPO ab CD4+ effector T cells. This study demonstrates that IL-17A produced by gd T cells plays a critical role in the pathogenesis of MPO-ANCA GN by promoting the development of MPO-specific ab T cells.
UR - http://www.scopus.com/inward/record.url?scp=85031995561&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1602025
DO - 10.4049/jimmunol.1602025
M3 - Article
C2 - 28954887
AN - SCOPUS:85031995561
VL - 199
SP - 3042
EP - 3050
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 9
ER -