Targeting Myeloid-Derived Suppressor Cells Is a Novel Strategy for Anti-Psoriasis Therapy.

Chao Chen,Lirong Tan,Li Lei,Xiang Chen,Jie Li,Panpan Liu,Cong Peng,Yehong Kuang,Wu Zhu

doi:10.1155/2020/8567320

Abstract

Psoriasis is a common immune-mediated, chronic inflammatory genetic-related disease that affects patients' quality of life. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of progenitor and immature myeloid cells which are expanded in psoriatic skin lesions and peripheral blood. However, the role of MDSCs in the pathogenesis of psoriasis remains unclear. Here, we confirmed that the accumulation of human MDSCs is remarkably increased in skin lesions of psoriasis patients by flow cytometry. Depleting MDSCs by Gemcitabine significantly suppresses IMQ-induced psoriatic inflammation and epidermal thickening as well as Th17 and Treg cell accumulation. Moreover, through the RNA-Seq technique, we validated some differentially expressed genes on CD4+ T-cells of IMQ-induced-MDSC-depleted mice such as IL-21 and Timd2, which are involved in Th17-cell differentiation or T-cell activation. Interestingly, neutralizing IL-21R by antibody reduces IMQ-induced epidermal thickening through downregulating the infiltration of MDSCs and Th17 cells. Our data suggest that targeting myeloid-derived suppressor cells is a novel strategy for antipsoriasis therapy. IL-21 may be a potential therapeutic target in psoriasis.

Highlights

Psoriasis is a common immune-mediated, chronic inflammatory skin disease, which has been characterized by epidermal acanthosis, hyperkeratosis, parakeratosis, and extensive inflammatory cell infiltration including T-lymphocytes, macrophages, mast cells, and neutrophils [1]
Accumulating evidence showed that the psoriatic keratinocytes (KCs) have been shown uncontrolled proliferation and respond to cytokines such as IL-22 or IL-17A/IL-17F released from Th17 or Th22 cells, which facilitate the secretion of proinflammatory factors such as AMP activating dendritic cells to initiate specific T-cell-related immune responses [1, 2]
Murine myeloid-derived suppressor cells (MDSCs) are characterized by coexpression of CD11b and Gr-1, whereas human MDSCs are most commonly identified by CD11b+ and CD33+ with low levels of HLA-DR, the major histocompatibility complex (MHC) class II molecule [7, 10]

Summary

Introduction

Psoriasis is a common immune-mediated, chronic inflammatory skin disease, which has been characterized by epidermal acanthosis, hyperkeratosis, parakeratosis, and extensive inflammatory cell infiltration including T-lymphocytes, macrophages, mast cells, and neutrophils [1]. Psoriatic KCs recruit immune cells into psoriatic skin lesions through the production of chemokines or cytokines including myeloid-derived suppressor cells (MDSCs) [3,4,5,6]. MDSCs (myeloid-derived suppressor cells) are a heterogeneous population of progenitor and immature myeloid cells, which have been generated during a variety of pathologic conditions such as cancer, infectious diseases, and autoimmune disorders [7,8,9]. Murine MDSCs are characterized by coexpression of CD11b and Gr-1, whereas human MDSCs are most commonly identified by CD11b+ and CD33+ with low levels of HLA-DR, the major histocompatibility complex (MHC) class II molecule [7, 10]. MDSCs consist of two large groups of cells: granulocytic or polymorphonuclear MDSCs (PMN-MDSCs, CD11b+CD14−CD15+CD33+HLA-DR−/lo)

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