Specific roles for dendritic cell subsets during initiation and progression of psoriasis

Abstract

Several subtypes of APCs are found in psoriasis patients, but their involvement in disease pathogenesis is poorly understood. Here, we investigated the contribution of Langerhans cells (LCs) and plasmacytoid DCs (pDCs) in psoriasis. In human psoriatic lesions and in a psoriasis mouse model (DKO* mice), LCs are severely reduced, whereas pDCs are increased. Depletion of pDCs in DKO* mice prior to psoriasis induction resulted in a milder phenotype, whereas depletion during active disease had no effect. In contrast, while depletion of Langerin-expressing APCs before disease onset had no effect, depletion from diseased mice aggravated psoriasis symptoms. Disease aggravation was due to the absence of LCs, but not other Langerin-expressing APCs. LCs derived from DKO* mice produced increased IL-10 levels, suggesting an immunosuppressive function. Moreover, IL-23 production was high in psoriatic mice and further increased in the absence of LCs. Conversely, pDC depletion resulted in reduced IL-23 production, and therapeutic inhibition of IL-23R signaling ameliorated disease symptoms. Therefore, LCs have an anti-inflammatory role during active psoriatic disease, while pDCs exert an instigatory function during disease initiation.

Crucial role of plasmacytoid dendritic cells in the development of acute colitis through the regulation of intestinal inflammation

“…As pDCs have shown to control certain immune responses through the production of IFN-I, [7][8][9][10][11][12][13][14] we assessed the contribution of the IFN-I signaling to the control of the development of acute DSS-induced colitis using Ifnar1 À / À mice, which lacking IFN-a/b receptor I (IFNAR1). 34 Unexpectively, there was no substantial difference in the BW loss between WT and Ifnar1 À / À mice following oral DSS administration (Supplementary Figure S2a).…”

“…[7][8][9] Therefore, pDCs have been considered as important mediators of antiviral responses. [7][8][9] Furthermore, recent studies have suggested that the activation of pDCs by recognition of self-NA causes elevated IFN-I levels, 10 and this process contributes to the induction of pathogenesis in psoriasis 11 and systemic lupus erythematosus (SLE). [12][13][14] The intestine is the largest compartment of the immune system that is lined by a single layer of epithelium harboring commensal bacteria.…”

Dynamics and Transcriptomics of Skin Dendritic Cells and Macrophages in an Imiquimod-Induced, Biphasic Mouse Model of Psoriasis

“…Activated dermal cDCs concomitantly migrate to skindraining lymph nodes (LNs), where they trigger the differentiation of autoantigen-specific naive T cells into skin-tropic effector T cells that are capable of secreting TNF-a, IFN-g, IL-17, or IL-22 and responsible for fueling the late phase of psoriasis (2). These cytokines contribute to increase the numbers of infiltrating neutrophils and stimulate keratinocytes to produce growth factors and inflammatory mediators (3)(4)(5)(6)(7).…”

Plasmacytoid Dendritic Cells Die by the CD8 T Cell–Dependent Perforin Pathway during Acute Nonviral Inflammation

“…Blocking pDC-dependent pathological mechanisms in these situations has been mostly associated with remission, suggesting that mechanisms controlling pDC survival, such as IFN-I, might be unpaired (7,9). Several mechanisms have been described for the control of the inflammatory immune response working in concert or independently, such as the limitation of Ag presentation through the killing of APC.…”