Gene

Cell biology

Biology

Innate lymphoid cell

T cell

Immunology

Genetics

FOXP3

Immune system

Interleukin 17

Medicine

Psoriasis

Innate immune system

RAR-related orphan receptor gamma

Phenotype

Nature Communications

Dysregulated IL-23/IL-17 responses have been linked to psoriatic arthritis and other forms of spondyloarthritides (SpA). RORγt, the key Thelper17 (Th17) cell transcriptional regulator, is also expressed by subsets of innate-like T cells, including invariant natural killer T (iNKT) and γδ-T cells, but their contribution to SpA is still unclear. Here we describe the presence of particular RORγt + T-bet lo PLZF − iNKT and γδ-hi T cell subsets in healthy peripheral blood. RORγt + iNKT and γδ-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 γδ-T cells showed unique and Th17-skewed phenotype and gene expression profiles. Strikingly, RORγt inhibition blocked γδ17 and iNKT17 cell function while selectively sparing IL-22 + subsets. Overall, our findings highlight a unique diversity of human RORγt + T cells and underscore the potential of RORγt antagonism to modulate aberrant type 17 responses.

RORγt inhibition selectively targets IL-17 producing iNKT and γδ-T cells enriched in Spondyloarthritis patients