Pro-inflammatory synovial fibroblasts contribute to chronic inflammation in joints in rheumatoid arthritis (RA); however, there are currently no approved therapies that target fibroblasts in RA. Therapeutic targeting of these cells requires an in-depth understanding of fibroblast heterogeneity in disease. A study by Zheng et al. provides a single-cell and spatial atlas of synovial cells in individuals with RA and identifies a subset of activated sub-lining fibroblasts that express integrin alpha 5 (ITGA5).

ITGA5+ fibroblasts promoted the migration of naive CD4+ T cells to the joint via the CCL5–CCR4 axis and induced the differentiation of these cells to PD-1hiCXCL13+ T effector cells via TGFβ1. PD-1hiCXCL13+ T effector cells resembled a previously reported T helper cell subset that expressed CXCL13, IL-21, ICOS and MAF, and could promote B cell responses in individuals with RA. Therefore, the authors hypothesized that ITGA5+ fibroblasts might be promoting pathogenic T cell responses in the joint.