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

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 blo...

Full description

Saved in:
Bibliographic Details
Main Authors: Chao Chen, Lirong Tan, Wu Zhu, Li Lei, Yehong Kuang, Panpan Liu, Jie Li, Xiang Chen, Cong Peng
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2020/8567320
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832566059399380992
author Chao Chen
Lirong Tan
Wu Zhu
Li Lei
Yehong Kuang
Panpan Liu
Jie Li
Xiang Chen
Cong Peng
author_facet Chao Chen
Lirong Tan
Wu Zhu
Li Lei
Yehong Kuang
Panpan Liu
Jie Li
Xiang Chen
Cong Peng
author_sort Chao Chen
collection DOAJ
description 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.
format Article
id doaj-art-486203a4e9ba44709012ccc74641c91f
institution Kabale University
issn 0962-9351
1466-1861
language English
publishDate 2020-01-01
publisher Wiley
record_format Article
series Mediators of Inflammation
spelling doaj-art-486203a4e9ba44709012ccc74641c91f2025-02-03T01:05:07ZengWileyMediators of Inflammation0962-93511466-18612020-01-01202010.1155/2020/85673208567320Targeting Myeloid-Derived Suppressor Cells Is a Novel Strategy for Anti-Psoriasis TherapyChao Chen0Lirong Tan1Wu Zhu2Li Lei3Yehong Kuang4Panpan Liu5Jie Li6Xiang Chen7Cong Peng8Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaPsoriasis 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.http://dx.doi.org/10.1155/2020/8567320
spellingShingle Chao Chen
Lirong Tan
Wu Zhu
Li Lei
Yehong Kuang
Panpan Liu
Jie Li
Xiang Chen
Cong Peng
Targeting Myeloid-Derived Suppressor Cells Is a Novel Strategy for Anti-Psoriasis Therapy
Mediators of Inflammation
title Targeting Myeloid-Derived Suppressor Cells Is a Novel Strategy for Anti-Psoriasis Therapy
title_full Targeting Myeloid-Derived Suppressor Cells Is a Novel Strategy for Anti-Psoriasis Therapy
title_fullStr Targeting Myeloid-Derived Suppressor Cells Is a Novel Strategy for Anti-Psoriasis Therapy
title_full_unstemmed Targeting Myeloid-Derived Suppressor Cells Is a Novel Strategy for Anti-Psoriasis Therapy
title_short Targeting Myeloid-Derived Suppressor Cells Is a Novel Strategy for Anti-Psoriasis Therapy
title_sort targeting myeloid derived suppressor cells is a novel strategy for anti psoriasis therapy
url http://dx.doi.org/10.1155/2020/8567320
work_keys_str_mv AT chaochen targetingmyeloidderivedsuppressorcellsisanovelstrategyforantipsoriasistherapy
AT lirongtan targetingmyeloidderivedsuppressorcellsisanovelstrategyforantipsoriasistherapy
AT wuzhu targetingmyeloidderivedsuppressorcellsisanovelstrategyforantipsoriasistherapy
AT lilei targetingmyeloidderivedsuppressorcellsisanovelstrategyforantipsoriasistherapy
AT yehongkuang targetingmyeloidderivedsuppressorcellsisanovelstrategyforantipsoriasistherapy
AT panpanliu targetingmyeloidderivedsuppressorcellsisanovelstrategyforantipsoriasistherapy
AT jieli targetingmyeloidderivedsuppressorcellsisanovelstrategyforantipsoriasistherapy
AT xiangchen targetingmyeloidderivedsuppressorcellsisanovelstrategyforantipsoriasistherapy
AT congpeng targetingmyeloidderivedsuppressorcellsisanovelstrategyforantipsoriasistherapy