Novel insights into dendritic cells in the pathogenesis of systemic sclerosis

Abstract

Summary Systemic sclerosis (SSc) is a severe autoimmune fibrotic disease characterized by fibrosis, vasculopathy, and immune dysregulation. Dendritic cells (DCs) are the most potent antigen‐presenting cells, specialized in pathogen sensing, with high capacity to shape the immune responses. The most recent technological advances have allowed the discovery of new DC subsets with potential implications in inflammatory conditions. Alterations of DC distribution in circulation and affected tissue as well as impaired DC function have been described in SSc patients, pointing towards a crucial role of these cells in SSc pathogenesis. In particular, recent studies have shown the importance of plasmacytoid DCs either by their high capacity to produce type I interferon or other inflammatory mediators implicated in SSc pathology, such as chemokine C‐X‐C motif ligand 4 (CXCL4). In‐vivo models of SSc have been vital to clarify the implications of DCs in this disease, especially DCs depletion and specific gene knock‐down studies. This review provides these new insights into the contribution of the different DCs subsets in the pathogenesis of SSc, as well as to the novel developments on DCs in in‐vivo models of SSc and the potential use of DCs and their mediators as therapeutic targets.

Fli1 deficiency suppresses RALDH1 activity of dermal dendritic cells and related induction of regulatory T cells: a possible role in scleroderma

“…Previous clinical and experimental studies on the role of DCs in SSc development have been predominantly focused on pDCs that contribute to sterile inflammation related to autoimmune rheumatic disorders through type I interferon (IFN-I) production in response to self-nucleic acids [8].…”

“…Among immune cells, previous research attention has focused on B cells, T cells and macrophages in SSc [7]. Regarding dendritic cells (DCs), recent studies have revealed the contribution of plasmacytoid DCs (pDCs) to the development of SSc [8], but the role of other DC subsets, such as conventional DCs (cDCs) and monocyte-derived DCs, had remained unknown. However, our recent study identified aldehyde dehydrogenase 1 (RALDH1)-producing CD103 − CD11b − cDCs as a critical DC subset regulating the development of inducible Foxp3 + regulatory T cells (Tregs) in BLM-treated mice and demonstrated decreased numbers of RALDH1-producing dermal DCs in SSc involved skin [9].…”

Innate immunity in systemic sclerosis

“…Carvalheiro et al . review the roles of dendritic cells in the pathogenesis of SSc [6]. Dendritic cells are the sentinels of the immune system, sensing their environment for antigen, and are the most potent antigen‐presenting cells promoting T cell activation, thus directing adaptive immunity.…”

The Roles of Immune Cells in the Pathogenesis of Fibrosis

“…Growing evidence indicates that dendritic cells (DCs) are novel players in the pathogenesis of various fibrotic diseases [ 55 , 56 ]. DCs are potent antigen-presenting cells with key roles in modulating immune responses.…”

“…The protective roles of tolerogenic DCs in cardiac fibrosis appear to be associated with reduced expressions of pro-inflammatory cytokines and increased IL-10 production [ 62 ]. Recent studies have suggested that pDCs are involved in SSc pathogenesis [ 56 ]. The pDCs infiltrated into the skin of SSc patients and produced large amounts of CXCL4 and IFN-α [ 63 ].…”