RORγt inhibition selectively targets pathogenic human iNKT and γδ-T cells enriched in Spondyloarthritis while preserving IL-22 responses — ASN Events
  1. Schedule
  2. Session 8: Autoimmunity and Tolerance
  3. RORγt inhibition selectively targets pathogenic human iNKT and γδ-T cells enriched in Spondyloarthritis while preserving IL-22 responses

RORγt inhibition selectively targets pathogenic human iNKT and γδ-T cells enriched in Spondyloarthritis while preserving IL-22 responses (#55)

Dirk Elewaut 1 , Koen Venken 2
  1. VIB Inflammation Research Center, Ghent University, Ghent, Belgium
  2. Laboratory for Molecular Immunology and Inflammation, Department of Rheumatology, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium

Dysregulated IL-23/IL-17 responses have been linked to inflammatory diseases including psoriasis, psoriatic arthritis and other forms of spondyloarthritides (SpA). IL-23/IL-17 inflammation is controlled by RORγt, the key Thelper17 (Th17) cell transcriptional regulator. RORγt is also expressed by subsets of innate-like T cells, including invariant natural killer T (iNKT) and γδ-T cells, but how this contributes to disorders such as SpA is still unclear.  Here we describe a unique population of RORγt+T-betloPLZF- iNKT and γδ-hi T cells present in healthy peripheral blood. iNKT and γδ-hi T cells showed profound IL-23 mediated Th17-like immune responses and were clearly enriched within inflamed joints. Unsupervised clustering analyses revealed a marked heterogeneity of human blood iNKT and γδ-T cells which seemed skewed in SpA patients.  Strikingly, RORγt inhibition blocked γδ17 and iNKT17 cell function while selectively sparing IL-22+ subsets. Overall, these findings highlight a unique diversity of human RORγt+ T cells and underscore the potential of RORγt antagonism to modulate aberrant type 17 responses.