Pathogenic stromal cells as therapeutic targets in joint inflammation

Abstract

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Anti‐TNF treatment negatively regulates human CD4+ T‐cell activation and maturation in vitro, but does not confer an anergic or suppressive phenotype

“…Synovial fibroblasts are particularly important in the context of RA given their role in the active invasion of articular cartilage and damage mediated by release of proinflammatory and matrixdegrading mediators (reviewed in ref. [36]). TNF-α is a strong inducer of fibroblast activation and is a key driver of inflammation www.eji-journal.eu and joint destruction; systemic over-expression of human TNF in vivo is sufficient to initiate chronic synovium inflammation, cartilage destruction, and bone erosion, which can be ameliorated by treatment with anti-TNF [37].…”

Coregistered Spectral Optical Coherence Tomography and Two‐Photon Microscopy for Multimodal Near‐Instantaneous Deep‐Tissue Imaging

“…We specifically focused in our work on target organs of chronic inflammation, especially relevant in the musculoskeletal system, that is, tendons and surrounding tissues in mouse paws, and on organs of the immune system: lymph nodes, spleens, bones, and bone marrow. As for the causes of tissue degeneration in tendons and joints, cells of mesenchymal origin such as fibroblasts, various mesenchymal stroma subtypes, endothelial cells, or tissue‐resident macrophages in the synovial membrane and in tendons are known to induce and maintain inflammation using diverse molecular and cellular mechanisms . In particular, tissue‐resident macrophages have a highly diverse range of biological functions.…”

Tissue inflammation signatures point towards resolution in adhesive capsulitis

“…Fibroblast activation markers PDPN and CD106 were highly expressed in both conditions, however CD90 was significantly reduced in frozen shoulder compared to tendon tears. CD90 (Thy1) is expressed by pathogenic synovial fibroblasts from Rheumatoid Arthritis patients with a pro-inflammatory and invasive phenotype [6,7]. The current study suggests the phenotypes of fibroblast subsets populating diseased shoulder tissues differ between self-limiting and persistent inflammation.…”