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

• DOI: 10.1038/s41467-017-01771-2
• Publication Date: 2017-11-09T12:34:25Z
• 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
• Keywords: Adult; Aged, 80 and over; CD4-Positive T-Lymphocytes; Male; 0303 health sciences; Science; Q; Granulocyte-Macrophage Colony-Stimulating Factor; Middle Aged; Article; Receptors, G-Protein-Coupled; 3. Good health; Mice; Young Adult; 03 medical and health sciences; Spondylarthritis; Animals; Humans; Female; Transcriptome; Aged; Genome-Wide Association Study

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