Piper, C; Pesenacker, AM; Bending, D; Thirugnanabalan, B; Varsani, H; Wedderburn, LR; Nistala, K; (2014) T cell GM-CSF expression in juvenile arthritis is contingent upon Th17 plasticity. Arthritis Rheumatol , 66 (7) pp. 1955-1960. 10.1002/art.38647.

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Abstract

Objectives Granulocyte monocyte colony stimulating factor (GM-CSF) is a potent inflammatory mediator responsible for recruitment and activation of innate immune cells. Recent murine data have identified Th17 cells as a key source of GM-CSF, and suggest that T cell derived GM-CSF is instrumental in the induction of autoimmune disease. We analysed the expression of T cell derived GM-CSF in the joints of patients with Juvenile idiopathic arthritis (JIA) and investigated the development links between Th17 and GM-CSF+ T helper cells. Methods 24 patients with JIA were analysed for expression of GM-CSF and the Th17 marker CD161 in synovial and peripheral blood compartments using flow cytometry and RT-PCR. A cytokine capture assay was used to purify Th17 cells and test the plasticity of cytokine production in response to IL-12 and IL-23. Results The frequency of GM-CSF producing T helper cells were significantly enriched in JIA synovial fluid mononuclear cells (SFMC) compared to PBMC (24.1% vs 2.9% of CD4+ T cells) and closely correlated with ESR levels (r(2) =0.91, p=<0.001). Synovial GM-CSF+ T cells were predominantly CD161 positive and co-expressed interferon gamma (IFNγ) but not IL-17. Culture of Th17 cells in the presence of IL-12 led to rapid upregulation of GM-CSF and IFNγ, recapitulating the phenotype of GM-CSF expressing cells within the joint. Conclusions Our results identify a novel outcome of Th17 plasticity in humans that may account for the enrichment of GM-CSF expressing T cells found within the JIA joint. The association of GM-CSF expression with systemic inflammation highlights the potential role for Th17 related cytokines in the pathology of JIA. © 2014 American College of Rheumatology.

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