ROR?t inhibition selectively targets IL-17 producing iNKT and ??-T cells enriched in Spondyloarthritis patients.

ABSTRACT: Dysregulated IL-23/IL-17 responses have been linked to psoriatic arthritis and other forms of spondyloarthritides (SpA). ROR?t, the key Thelper17 (Th17) cell transcriptional regulator, is also expressed by subsets of innate-like T cells, including invariant natural killer T (iNKT) and ??-T cells, but their contribution to SpA is still unclear. Here we describe the presence of particular ROR?t⁺T-bet^loPLZF^- iNKT and ??-hi T cell subsets in healthy peripheral blood. ROR?t⁺ iNKT and ??-hi T cells show IL-23 mediated Th17-like immune responses and were clearly enriched within inflamed joints of SpA patients where they act as major IL-17 secretors. SpA derived iNKT and ??-T cells showed unique and Th17-skewed phenotype and gene expression profiles. Strikingly, ROR?t inhibition blocked ??17 and iNKT17 cell function while selectively sparing IL-22⁺ subsets. Overall, our findings highlight a unique diversity of human ROR?t⁺ T cells and underscore the potential of ROR?t antagonism to modulate aberrant type 17 responses.

SUBMITTER: Venken K 

PROVIDER: S-EPMC6315029 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature