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SAT0250 TH17 cells expressing KIR3DL2 and enriched for gut homing markers are increased in ankylosing spondylitis
  1. A. Ridley1,
  2. S. Kollnberger2,
  3. I. Wong1,
  4. J. Shaw2,
  5. P. Bowness2
  1. 1Weatherall Institute of Molecular Medicine
  2. 2Ndorms, Botnar Institute, University of Oxford, Oxford, United Kingdom

Abstract

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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