Dysregulated IL-23/IL-17 responses have been linked to psoriatic arthritis and other forms of spondyloarthritides (SpA). RORt, 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 how they contribute to disorders such as SpA is still unclear. Here we describe the presence of particular RORt+T-betloPLZF- iNKT and -hi T cell subsets in healthy peripheral blood. RORt+ iNKT and -hi T cells showed profound 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 a unique Th17 skewed phenotype and gene expression profile. Strikingly, RORt inhibition blocked 17 and iNKT17 cell function while selectively sparing IL-22+ subsets. Overall, these findings highlight a unique diversity of human RORt+ T cells and underscore the potential of RORt antagonism to modulate aberrant type 17 responses. SOURCE: Liesbet Martens (liesbet.martens@irc.vib-ugent.be) -  VIB-University of Ghent

Pluto Bioinformatics

GSE122624: RORt inhibition selectively targets IL-17 producing human iNKT and -T cells enriched in Spondyloarthritis while preserving IL-22 responses