Myeloid-Derived Suppressor Cells in Psoriasis Are an Expanded Population Exhibiting Diverse T-Cell–Suppressor Mechanisms

Abstract

Psoriasis vulgaris is an inflammatory skin disease caused by hyper-activated T-cells regulated by positive and negative mechanisms; while the former has been much studied, but the latter has not. We studied the regulatory mechanism mediated by myeloid-derived suppressor cells (MDSCs), especially having shown that MDSCs expanded in melanoma patients express DC-HIL, a critical mediator of T-cell suppressor function. We examined expansion of DC-HIL+ MDSCs in psoriasis and characterized their functional properties. Frequency of DC-HIL+ monocytic MDSCs (CD14+HLA-DRno/low) in blood and skin was markedly increased in psoriatic patients vs. healthy controls, but there was no statistically significant relationship with disease severity (PASI score). Blood DC-HIL+ MDSC levels in the untreated patients were significantly higher than the treated patients. Compared to melanoma-derived MDSCs, psoriatic MDSCs exhibited significantly reduced suppressor function, and were less dependent on DC-HIL, but capable of inhibiting proliferation and IFN-γ and IL-17 responses of autologous T-cells. Psoriatic MDSCs were functionally diverse among patients in their ability to suppress allogeneic T-cells and use of either IL-17/arginase I or IFN-γ/iNOS axis as suppressor mechanisms. Thus DC-HIL+ MDSCs are expanded in psoriasis patients, and their mechanistic heterogeneity and relative functional deficiency may contribute to the development of psoriasis.

CXCL17 Attenuates Imiquimod-Induced Psoriasis-like Skin Inflammation by Recruiting Myeloid-Derived Suppressor Cells and Regulatory T Cells

“…Only limited numbers of previous reports discussed suppressive function of MDSCs in inflammatory disorders such as alopecia areata and arthritis (46)(47)(48). Very recently, MDSCs were reported to be expanded in psoriasis, infiltrating into lesional skin (49). They concluded that MDSC-mediated immunosuppression contributed to regulating hyperactivated T cells in psoriatic skin, which our results completely supported.…”

Phenotypic and functional alterations of myeloid‐derived suppressor cells during the disease course of multiple sclerosis

“…MDSCs have important T-cell regulatory functions and have been suggested as a promising target in the development of novel therapeutics for MS. 10,17 However, current knowledge on the role of MDSCs in autoimmune diseases is limited and previous findings have been discordant. 12,13,15,17 Within the present study, we report data demonstrating differences in the frequency and absolute number of MDSC populations during the MS disease course, with addition changes to the functional status of Mo-MDSCs, including a loss in T-cell suppressive action, during progression of disease.…”

“…Interestingly, in contrast to the situation in tumors, MDSC function in autoimmune diseases may involve both immunosuppressive and proinflammatory functions . A recent study reported that Mo‐MDSCs within the peripheral blood of patients with psoriasis exert reduced T‐cell suppressive ability, compared to melanoma‐derived Mo‐MDSCs . Similarly, Mo‐MDSCs derived from patients with inflammatory bowel disease failed to suppress T cells, which was associated with downregulation of CCAAT/enhancer‐binding protein beta (CEBP‐β) expression .…”

“…9,[12][13][14] A recent study reported that Mo-MDSCs within the peripheral blood of patients with psoriasis exert reduced T-cell suppressive ability, compared to melanoma-derived Mo-MDSCs. 15 Similarly, Mo-MDSCs derived from patients with inflammatory bowel disease failed to suppress T cells, which was associated with downregulation of CCAAT/enhancerbinding protein beta (CEBP-b) expression. 14 Mo-MDSCs respond to their local environmental milieu, modulating their function in response to stimulation.…”

Spatholobus Suberectus Column Extract Suppresses Dendritic Cell Maturation and has Therapeutic Potential for Psoriasis

“…DC-induced cytokine production subsequently stimulated T-cell activity [4]. A cross-talk between DCs and T cells is thought to be responsible for the disease development [5]. Recently, the clearance of psoriasis using targeted immunotherapies demonstrates the important role of DCs in the pathogenesis of psoriasis.…”