Pathogenic role for γδ T cells in autoimmune anti-myeloperoxidase glomerulonephritis

Research output: Contribution to journalArticleResearchpeer-review

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 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.

Original languageEnglish
Pages (from-to)3042-3050
Number of pages9
JournalJournal of Immunology
Volume199
Issue number9
DOIs
Publication statusPublished - 1 Nov 2017

Cite this

@article{c06680a6487b4db795cd9645ae1357aa,
title = "Pathogenic role for γδ T cells in autoimmune anti-myeloperoxidase 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 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.",
author = "Gan, {Poh Yi} and Takeshi Fujita and Ooi, {Joshua Daniel} and Alikhan, {Maliha Asghar} and Jonathan Dick and Raymond Shim and Dragana Odobasic and O'Sullivan, {Kim Maree} and Kitching, {Arthur Richard} and Holdsworth, {Stephen Roger}",
year = "2017",
month = "11",
day = "1",
doi = "10.4049/jimmunol.1602025",
language = "English",
volume = "199",
pages = "3042--3050",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "9",

}

Pathogenic role for γδ T cells in autoimmune anti-myeloperoxidase glomerulonephritis. / Gan, Poh Yi; Fujita, Takeshi; Ooi, Joshua Daniel; Alikhan, Maliha Asghar; Dick, Jonathan; Shim, Raymond; Odobasic, Dragana; O'Sullivan, Kim Maree; Kitching, Arthur Richard; Holdsworth, Stephen Roger.

In: Journal of Immunology, Vol. 199, No. 9, 01.11.2017, p. 3042-3050.

Research output: Contribution to journalArticleResearchpeer-review

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.

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U2 - 10.4049/jimmunol.1602025

DO - 10.4049/jimmunol.1602025

M3 - Article

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SP - 3042

EP - 3050

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

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