Mesenchymal Stem Cells Alleviate Moderate-to-Severe Psoriasis by Reducing the Production of Type I Interferon (IFN-I) by Plasmacytoid Dendritic Cells (pDCs)

Maosheng Chen,Ge Lin,Na Xiao,Jia Zhou,Yeping Lu,Jing Peng,Lamei Cheng,Chuang Li,Yanni Dai,Qi Xie,Xian Su,Hua Mei,Siqi Wang

doi:10.1155/2019/6961052

Abstract

The anti-inflammatory and immunomodulatory properties of mesenchymal stem cells (MSCs) have been proposed to be involved in some autoimmune diseases and have been successfully tested in patients and mice. But their contribution to psoriasis and the underlying mechanisms involved remains elusive. Here, we explored the feasibility of using human umbilical cord-derived MSC (hUC-MSC) infusion as a therapeutic approach in an imiquimod- (IMQ-) induced psoriasis mouse model. MSC infusion were found to significantly reduce the severity and development of psoriasis, inhibit the infiltration of immune cells to the skin, and downregulate the expression of several proinflammatory cytokines and chemokines. Our results provide an explanation for the therapeutic effects of MSC infusion by first suppressing neutrophil function and then downregulating the production of type I interferon (IFN-I) by plasmacytoid dendritic cells (pDCs). Therefore, we discovered a novel mechanism of stem cell therapy for psoriasis. In summary, our results showed that MSC infusion could be an effective and safe treatment for psoriasis.

Highlights

Psoriasis is a common relapsing and remitting immunemediated inflammatory disease that affects the skin, joints, and other organs
To better understand the role of mesenchymal stem cells (MSCs) infusion in psoriasis pathogenesis, IMQ was topically applied to mice daily for 6 consecutive days and they were injected intravenously with MSCs after the 6th day of IMQ
When flow cytometry was used to analyze the percentage of Th1, Th2, and Th17 cytokine-positive cells, we found that the proportion of Th1 cells and Th17 cells was decreased after the MSC infusions, while the proportion of Th2 cells was slightly increased indicating that the MSCs had immunomodulatory and anti-inflammatory properties

Summary

Introduction

Psoriasis is a common relapsing and remitting immunemediated inflammatory disease that affects the skin, joints, and other organs. The prevalence of psoriasis is about 2% to 3% of the world’s population. The most common disease subtype, is seen in approximately 85% of cases and commonly manifests as a well-demarcated, erythematous, and raised lesion with silvery scales [1, 2]. T cells proliferate and migrate into the epidermis, where they recognize epidermal autoantigens and produce IL-22 and IL-17 [8,9,10]. The Th17 cytokines drive the development of the psoriatic phenotype by inducing epidermal hyperproliferation and activating keratinocytes to produce cytokines and chemokines, which sustain and amplify the inflammatory process [11, 12]

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