Unique transcriptome signatures and GM-CSF expression in lymphocytes from patients with spondyloarthritis

被引：122

作者：

Al-Mossawi, M. H. ^{[1
]}

Chen, L. ^{[1
]}

Fang, H. ^{[2
]}

Ridley, A. ^{[1
]}

de Wit, J. ^{[1
]}

Yager, N. ^{[1
]}

Hammitzsch, A. ^{[1
]}

Pulyakhina, I. ^{[2
]}

Fairfax, B. P. ^{[2
]}

Simone, D. ^{[1
]}

Yi, Yao ^{[1
]}

Bandyopadhyay, S. ^{[1
]}

Doig, K. ^{[1
]}

Gundle, R. ^{[1
]}

Kendrick, B. ^{[1
]}

Powrie, F. ^{[3
]}

Knight, J. C. ^{[2
]}

Bowness, P. ^{[1
]}

机构：

[1] Univ Oxford, Botnar Res Ctr, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Oxford OX3 7LD, England

[2] Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Old Rd Campus, Oxford OX3 7BN, England

[3] Univ Oxford, Kennedy Inst Rheumatol, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Oxford OX3 7FY, England

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

英国惠康基金; 巴西圣保罗研究基金会; 加拿大创新基金会;

关键词：

INNATE LYMPHOID-CELLS; COLONY-STIMULATING FACTOR; ANKYLOSING-SPONDYLITIS; T-CELLS; CLASSIFICATION CRITERIA; INFLAMMATORY ARTHRITIS; PSORIATIC-ARTHRITIS; T(H)17 CELLS; DOUBLE-BLIND; AUTOIMMUNE;

D O I：

10.1038/s41467-017-01771-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Spondyloarthritis encompasses a group of common inflammatory diseases thought to be driven by IL-17A-secreting type-17 lymphocytes. Here we show increased numbers of GM-CSF- producing CD4 and CD8 lymphocytes in the blood and joints of patients with spondy-loarthritis, and increased numbers of IL-17A(+)GM-CSF+ double-producing CD4, CD8, gamma delta and NK cells. GM-CSF production in CD4 T cells occurs both independently and in combination with classical Th1 and Th17 cytokines. Type 3 innate lymphoid cells producing predominantly GM-CSF are expanded in synovial tissues from patients with spondyloarthritis. GM-CSF(+)CD4(+) cells, isolated using a triple cytokine capture approach, have a specific transcriptional signature. Both GM-CSF+ and IL-17A(+) GM-CSF+ double-producing CD4 T cells express increased levels of GPR65, a proton-sensing receptor associated with spondyloarthritis in genome-wide association studies and pathogenicity in murine inflammatory disease models. Silencing GPR65 in primary CD4 T cells reduces GM-CSF production. GM-CSF and GPR65 may thus serve as targets for therapeutic intervention of spondyloarthritis.

引用

页数：11

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