Dendritic cell heterogeneity and its role in connective tissue diseases

Abstract

By balancing immunity and tolerance, dendritic cells (DCs) are key regulators of immune responses. Recent studies have highlighted the crucial role of these cells in connective tissue diseases. Conventional DCs (cDCs) and plasmacytoid DCs (pDCs) exhibit distinct contributions to disease progression. In systemic lupus erythematosus and systemic sclerosis, pDCs primarily drive pathogenesis via excessive type I interferon production, whereas in rheumatoid arthritis (RA), cDCs play a major role in promoting autoreactive T cell activation. Emerging DC subsets, such as inflammatory DC3s and LAMP3+ DCs, have been implicated in RA synovitis. In vasculitis, tissue-resident vascular DCs appear to regulate localized inflammation. Despite advances in single-cell analysis, the functional roles of specific DC subsets remain underexplored in several autoimmune conditions. Understanding DC heterogeneity and function in disease-specific contexts may lead to novel therapeutic strategies targeting DC-mediated immune dysregulation.