Table 4_Single cell RNA-sequencing identified CCR7+/RELB+/IRF1+ T cell responding for juvenile idiopathic arthritis pathogenesis.docx

BackgroundTo further explore the disease heterogeneity of different subtypes of Juvenile idiopathic arthritis (JIA) and analyze their pathogenesis mechanisms.
MethodThe single-cell RNA sequencing (scRNA-seq) analysis of peripheral blood mononuclear cells (PBMCs) was carried out to investigate the disease heterogeneity and molecular mechanisms of immune responses in immune cells in JIA.
ResultIn our study, we provided a immunological landscape of HLA-B27-positive JIA and HLA-B27-negative JIA immune cells at single cell RNA-Seq resolution. We found a higher proportion of CCR7+/RELB+/IRF1+ triple positive T cells in the peripheral blood of patients with JIA, and such T cells were predominantly present in HLA-B27+ JIA patients. Furthermore, we hypothesized that CCR7+/RELB+/IRF1+ triple positive T cells were highly activated T cells capable of promoting the differentiation of osteoclasts by producing IL-17, thus causing damage to cartilage in HLA-B27+ JIA patients. Unlike JIA patients, CCR7+/RELB+/IRF1+ triple positive T cells were not found in the peripheral blood of pSS patients and SLE patients, moreover, T cells from pSS patients and SLE patients were less able to produce IL-17 than those from JIA patients.
ConclusionOur study provided evidence of cellular and molecular levels of involvement in JIA pathogenesis and identified the critical roles for T cells in JIA pathogenesis. Furthermore, our results suggested that there were significant differences in T cell composition and gene expression between HLA-B27+ JIA patients and HLA-B27- JIA patients. Our findings indicated that CCR7+/RELB+/IRF1+ positive T cells could damage the cartilage of HLA-B27+ JIA by producing cytokines such as IL-17.