Unique Transcriptome Signatures and GM-CSF Expression in Lymphocytes from Patients with Spondyloarthritis

Overview

Journal Nat Commun

Specialty Biology

Date 2017 Nov 17

PMID 29142230

Citations 74

Authors

M H Al-Mossawi

L Chen

H Fang

A Ridley

J de Wit

N Yager

A Hammitzsch

I Pulyakhina

B P Fairfax

D Simone

Yao Yi

S Bandyopadhyay

K Doig

R Gundle

B Kendrick

F Powrie

J C Knight

P Bowness

Affiliations

Soon will be listed here.

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-17AGM-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-CSFCD4 cells, isolated using a triple cytokine capture approach, have a specific transcriptional signature. Both GM-CSF and IL-17AGM-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.

Citing Articles

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