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

Abstract：

: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 spondyloarthritis, and increased numbers of IL-17A+GM-CSF+ double-producing CD4, CD8, γδ 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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Al-Mossawi MH,Chen L,Fang H,Ridley A,de Wit J,Yager N,Hammitzsch A,Pulyakhina I,Fairfax BP,Simone D,Yi Y,Bandyopadhyay S,Doig K,Gundle R,Kendrick B,Powrie F,Knight JC,Bowness P

doi

10.1038/s41467-017-01771-2

subject

Has Abstract

pub_date

2017-11-15 00:00:00

pages

1510

issue

1

issn

2041-1723

pii

10.1038/s41467-017-01771-2

journal_volume

8

pub_type

杂志文章

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