Background T helper 17 (Th17) cells are a subset of pro-inflammatory CD4 T cells implicated in a number of inflammatory arthritides including the Spondyloarthritides (SpAs). Ankylosing Spondylitis (AS), the commonest spondyloarthropathy, is genetically associated with HLA-B27 (B27) and IL-23 receptor polymorphisms, however the link remains unexplained. We have previously shown KIR3DL2+CD4 T cells are expanded in the peripheral blood of individuals with AS.
Objectives The aim of the study was to further characterize KIR3DL2+CD4 T cells and investigate whether activation induced expression of KIR3DL2 on CD4 T cells.
Methods KIR3DL2+ CD4 T cell phenotype was investigated by flow cytometry. Production of cytokines by PMA/ionomycin stimulated-PBMCs was investigated by intracellular cytokine staining (ICS). Cytokine production by α-CD3/28-stimulated FACS-sorted KIR3DL2+ and KIR3DL2- CD4 T cells was investigated by multiplex bead analysis. Expression of KIR3DL2+ on CD4 T cells was investigated after SEB stimulation and cytokine production was investigated by ELISA.
Results KIR3DL2+ CD4 T cells, increased in peripheral blood of HLA-B27+ SpA patients, were enriched for expression of Th17 phenotypic markers, IL-23R, CCR6 and IL-1R, and the gut-homing chemokine receptor, CCR9. KIR3DL2+ CD4 T cells from AS patients produced significantly more IL-17 than KIR3DL2- CD4 T cells. IL-17 levels significantly increased in the presence of the Th17 cytokines rIL-23 and IL-1. SEB activation increased the number of KIR3DL2+ cells and IL-17 production more in AS patients than controls.
Conclusions KIR3DL2+ CD4 Th17 cells are expanded in patients with Spondyloarthritis. Expression of KIR3DL2 on CD4 T cells can be induced by activation. These cells constitute a significant proportion of peripheral blood CD4 T IL-23R-expressing cells and produce increased levels of IL-17, which is further increased by the presence of Th17 cytokines. Our findings would support the trial of new therapeutic strategies, such as anti-IL-17, in AS/SpA.
Disclosure of Interest None Declared
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