Disease-specific expansion of CD29+IL-17RA+ T effector cells possessing multiple signalling pathways in spondyloarthritis

Abstract

Objectives T cells adhere to enthesis fibrocartilage via integrins and intrinsically require IL-17RA-mediated signals to maintain their effector function. We analyzed CD29+IL-17RA+T cells in inflamed lesions and peripheral blood in patients with spondyloarthritis (SpA) and investigated their association with disease activity and therapeutic response. Methods Transcriptome analysis of synovial fluid T cells from psoriatic arthritis was performed by publicly available bulk-cell RNA-sequencing data. Blood samples were obtained from healthy controls (n = 37), rheumatoid arthritis (RA, n = 12), IgG4-related disease (IgG4-RD, n = 12), large vessel vasculitis (LVV, n = 12), and SpA (n = 28) and were analyzed by flow cytometry. Results T cells in the inflamed joints of psoriatic arthritis showed CD29 and IL-17RA expression. CD29+IL-17RA+ T cells showed enriched CXCR3+CD45RA+ effector cells and activation of the spleen tyrosine kinase (Syk), nuclear factor κB (NF-κB), and Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathways. The proportion of peripheral blood CD29+IL-17RA+ T cells was significantly increased in patients with SpA than in patients with RA, IgG4-RD, or LVV and in healthy controls. Based on the ASDAS-CRP scores, the proportion of CD29+IL-17RA+ T cells was positively correlated with disease activity in treatment-naïve patients with active SpA. Anti-IL-17 but not anti-TNF monoclonal antibodies reduced CD29+IL-17RA+ T cells. Conclusions CD29+IL-17RA+ T effector cells with enhanced Syk, NF-κB, and JAK-STAT pathways was specifically increased in SpA and was correlated with disease activity, implicating a role of this newly identified T cell population in the pathogenesis. Anti-IL-17 monoclonal antibodies may be effective for patients by reducing this pathogenic T cell population.