Generation of a T cell receptor, cytokine and cell repertoire synovial fluid atlas to define commonalities and dissimilarities between arthritic diseases through systems immunology approaches

Korte inhoud:Although different chronic arthritic diseases are defined by clinical factors like gender, psoriasis and auto-antibodies, the biology of joint inflammation across this disease spectrum remains understudied. Leveraging our novel TRIASSIC tool and a newly curated T-cell receptor (TCR) database derived from inflamed joints, we identified 66303 significantly convergent TCR clonotypes. Clustering TCR clonotypes showed that synovial fluid convergence clusters (SFCCs) distinctly characterized HLA-B27+ mediated diseases (ankylosing spondylitis, AS and enthesitis-related juvenile idiopathic arthritis, JIA-ERA), Lyme arthritis and oligoarticular JIA. Single-cell transcriptomics and bulk proteomics showed upregulated interferon type I and II and TNF-α pathways in oJIA. Adult and juvenile psoriatic arthritis, (JIA-)PsA, exhibited increased expression of HSP in monocytes and TXNIP in T-cells. HLA-B27+ JIA-ERA and AS had abundant CCL5-expressing CD8+ T-cells, with JIA-ERA showing CD74 and LGALS1 upregulation in Th1/Th17 cells and IGHV7-4.1 in B-cells. oJIA uniquely shared a TRBV28 RG-motif on CXCL13-producing helper T-cells while rheumatoid arthritis and (JIA-)PsA harboured EBV-reactive cytotoxic CD8+ T-cells. Annexin signalling was critical for intercellular communication across all arthritis groups. These findings highlight both disease-specific and broadly shared mechanisms in chronic arthritis.

Jaar van publicatie:2025

Trefwoorden:Biology

Toegankelijkheid:Open