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RORγt inhibition selectively targets IL-17 producing iNKT and γδ-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). 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-betloPLZF- 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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Venken K,Jacques P,Mortier C,Labadia ME,Decruy T,Coudenys J,Hoyt K,Wayne AL,Hughes R,Turner M,Van Gassen S,Martens L,Smith D,Harcken C,Wahle J,Wang CT,Verheugen E,Schryvers N,Varkas G,Cypers H,Wittoek R,Piette Y

doi

10.1038/s41467-018-07911-6

subject

Has Abstract

pub_date

2019-01-02 00:00:00

pages

9

issue

1

issn

2041-1723

pii

10.1038/s41467-018-07911-6

journal_volume

10

pub_type

杂志文章

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