PMID- 28954887 OWN - NLM STAT- MEDLINE DCOM- 20171026 LR - 20180129 IS - 1550-6606 (Electronic) IS - 0022-1767 (Linking) VI - 199 IP - 9 DP - 2017 Nov 1 TI - Pathogenic Role for gammadelta T Cells in Autoimmune Anti-Myeloperoxidase Glomerulonephritis. PG - 3042-3050 LID - 10.4049/jimmunol.1602025 [doi] 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 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. CI - Copyright (c) 2017 by The American Association of Immunologists, Inc. FAU - Gan, Poh-Yi AU - Gan PY AUID- ORCID: 0000-0001-8373-7144 AD - Centre for Inflammatory Diseases, Department of Medicine, Monash Medical Centre, Monash University, Clayton, Victoria 3168, Australia; Poh-yi.gan@monash.edu. AD - Department of Immunology, Monash Health, Monash Medical Centre, Clayton, Victoria 3168, Australia. FAU - Fujita, Takeshi AU - Fujita T AUID- ORCID: 0000-0001-8856-4385 AD - Department of Cardiology, Respiratory Medicine and Nephrology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan; and. FAU - Ooi, Joshua Daniel AU - Ooi JD AD - Centre for Inflammatory Diseases, Department of Medicine, Monash Medical Centre, Monash University, Clayton, Victoria 3168, Australia. FAU - Alikhan, Maliha Asghar AU - Alikhan MA AUID- ORCID: 0000-0002-2578-3457 AD - Centre for Inflammatory Diseases, Department of Medicine, Monash Medical Centre, Monash University, Clayton, Victoria 3168, Australia. FAU - Dick, Jonathan AU - Dick J AUID- ORCID: 0000-0003-4012-9610 AD - Centre for Inflammatory Diseases, Department of Medicine, Monash Medical Centre, Monash University, Clayton, Victoria 3168, Australia. AD - Department of Nephrology, Monash Health, Monash Medical Centre, Clayton, Victoria 3168, Australia. FAU - Shim, Raymond AU - Shim R AD - Centre for Inflammatory Diseases, Department of Medicine, Monash Medical Centre, Monash University, Clayton, Victoria 3168, Australia. FAU - Odobasic, Dragana AU - Odobasic D AD - Centre for Inflammatory Diseases, Department of Medicine, Monash Medical Centre, Monash University, Clayton, Victoria 3168, Australia. FAU - O'Sullivan, Kim Maree AU - O'Sullivan KM AUID- ORCID: 0000-0002-3098-7948 AD - Centre for Inflammatory Diseases, Department of Medicine, Monash Medical Centre, Monash University, Clayton, Victoria 3168, Australia. FAU - Kitching, Arthur Richard AU - Kitching AR AUID- ORCID: 0000-0002-2713-2391 AD - Centre for Inflammatory Diseases, Department of Medicine, Monash Medical Centre, Monash University, Clayton, Victoria 3168, Australia. AD - Department of Nephrology, Monash Health, Monash Medical Centre, Clayton, Victoria 3168, Australia. FAU - Holdsworth, Stephen Roger AU - Holdsworth SR AD - Centre for Inflammatory Diseases, Department of Medicine, Monash Medical Centre, Monash University, Clayton, Victoria 3168, Australia. AD - Department of Immunology, Monash Health, Monash Medical Centre, Clayton, Victoria 3168, Australia. AD - Department of Nephrology, Monash Health, Monash Medical Centre, Clayton, Victoria 3168, Australia. LA - eng PT - Journal Article DEP - 20170927 PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Autoantibodies) RN - 0 (Il17a protein, mouse) RN - 0 (Interleukin-17) RN - 0 (Receptors, Antigen, T-Cell, alpha-beta) RN - 0 (Receptors, Antigen, T-Cell, gamma-delta) RN - EC 1.11.1.7 (Peroxidase) SB - IM MH - Animals MH - Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/genetics/immunology/pathology MH - Autoantibodies/genetics/immunology MH - Autoimmune Diseases/genetics/*immunology/pathology MH - CD4-Positive T-Lymphocytes/*immunology/pathology MH - Glomerulonephritis/genetics/*immunology/pathology MH - Interleukin-17/genetics/immunology MH - Mice MH - Mice, Knockout MH - Peroxidase/genetics/*immunology MH - Receptors, Antigen, T-Cell, alpha-beta/genetics/immunology MH - Receptors, Antigen, T-Cell, gamma-delta/genetics/*immunology EDAT- 2017/09/29 06:00 MHDA- 2017/10/27 06:00 CRDT- 2017/09/29 06:00 PHST- 2016/11/30 00:00 [received] PHST- 2017/08/24 00:00 [accepted] PHST- 2017/09/29 06:00 [pubmed] PHST- 2017/10/27 06:00 [medline] PHST- 2017/09/29 06:00 [entrez] AID - jimmunol.1602025 [pii] AID - 10.4049/jimmunol.1602025 [doi] PST - ppublish SO - J Immunol. 2017 Nov 1;199(9):3042-3050. doi: 10.4049/jimmunol.1602025. Epub 2017 Sep 27.