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Acitretin Promotes the Differentiation of Myeloid-Derived Suppressor Cells in the Treatment of Psoriasis

Increased numbers of myeloid-derived suppressor cells (MDSCs) are involved in the development of psoriasis. Acitretin is used to treat psoriasis by regulating the proliferation and differentiation of keratinocytes, but little is known about the effect of acitretin on immune cells. Here, we reported...

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Autores principales: Liu, Panpan, Peng, Cong, Chen, Xiang, Wu, Lisha, Yin, Mingzhu, Li, Jie, Qin, Qunshi, Kuang, Yehong, Zhu, Wu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021725/
https://www.ncbi.nlm.nih.gov/pubmed/33834031
http://dx.doi.org/10.3389/fmed.2021.625130
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author Liu, Panpan
Peng, Cong
Chen, Xiang
Wu, Lisha
Yin, Mingzhu
Li, Jie
Qin, Qunshi
Kuang, Yehong
Zhu, Wu
author_facet Liu, Panpan
Peng, Cong
Chen, Xiang
Wu, Lisha
Yin, Mingzhu
Li, Jie
Qin, Qunshi
Kuang, Yehong
Zhu, Wu
author_sort Liu, Panpan
collection PubMed
description Increased numbers of myeloid-derived suppressor cells (MDSCs) are involved in the development of psoriasis. Acitretin is used to treat psoriasis by regulating the proliferation and differentiation of keratinocytes, but little is known about the effect of acitretin on immune cells. Here, we reported that psoriasis patients had an expansion of MDSCs and monocytic-MDSCs (M-MDSCs) in peripheral blood and skin lesions. The number of MDSCs and M-MDSCs in peripheral blood correlated positively with disease severity. Acitretin could reduce the number of MDSCs and M-MDSCs in the peripheral blood of psoriasis patients as well as the spleen and skin lesions of IMQ-induced psoriasis-like model mice. Moreover, acitretin promoted the differentiation of MDSCs into macrophages, especially CD206(+) M2 macrophages, and CD11c(+)MHC-II(+) dendritic cells. Mechanically, acitretin dramatically increased the glutathione synthase (GSS) expression and glutathione (GSH) accumulation in MDSCs. Interruption of GSH synthesis abrogated the acitretin effect on MDSCs differentiation. Acitretin regulated GSS expression via activation of extracellular signal-regulated kinase 1/2. Thus, our data demonstrated a novel mechanism underlying the effects of acitretin on psoriasis by promoting MDSCs differentiation.
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spelling pubmed-80217252021-04-07 Acitretin Promotes the Differentiation of Myeloid-Derived Suppressor Cells in the Treatment of Psoriasis Liu, Panpan Peng, Cong Chen, Xiang Wu, Lisha Yin, Mingzhu Li, Jie Qin, Qunshi Kuang, Yehong Zhu, Wu Front Med (Lausanne) Medicine Increased numbers of myeloid-derived suppressor cells (MDSCs) are involved in the development of psoriasis. Acitretin is used to treat psoriasis by regulating the proliferation and differentiation of keratinocytes, but little is known about the effect of acitretin on immune cells. Here, we reported that psoriasis patients had an expansion of MDSCs and monocytic-MDSCs (M-MDSCs) in peripheral blood and skin lesions. The number of MDSCs and M-MDSCs in peripheral blood correlated positively with disease severity. Acitretin could reduce the number of MDSCs and M-MDSCs in the peripheral blood of psoriasis patients as well as the spleen and skin lesions of IMQ-induced psoriasis-like model mice. Moreover, acitretin promoted the differentiation of MDSCs into macrophages, especially CD206(+) M2 macrophages, and CD11c(+)MHC-II(+) dendritic cells. Mechanically, acitretin dramatically increased the glutathione synthase (GSS) expression and glutathione (GSH) accumulation in MDSCs. Interruption of GSH synthesis abrogated the acitretin effect on MDSCs differentiation. Acitretin regulated GSS expression via activation of extracellular signal-regulated kinase 1/2. Thus, our data demonstrated a novel mechanism underlying the effects of acitretin on psoriasis by promoting MDSCs differentiation. Frontiers Media S.A. 2021-03-23 /pmc/articles/PMC8021725/ /pubmed/33834031 http://dx.doi.org/10.3389/fmed.2021.625130 Text en Copyright © 2021 Liu, Peng, Chen, Wu, Yin, Li, Qin, Kuang and Zhu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
Liu, Panpan
Peng, Cong
Chen, Xiang
Wu, Lisha
Yin, Mingzhu
Li, Jie
Qin, Qunshi
Kuang, Yehong
Zhu, Wu
Acitretin Promotes the Differentiation of Myeloid-Derived Suppressor Cells in the Treatment of Psoriasis
title Acitretin Promotes the Differentiation of Myeloid-Derived Suppressor Cells in the Treatment of Psoriasis
title_full Acitretin Promotes the Differentiation of Myeloid-Derived Suppressor Cells in the Treatment of Psoriasis
title_fullStr Acitretin Promotes the Differentiation of Myeloid-Derived Suppressor Cells in the Treatment of Psoriasis
title_full_unstemmed Acitretin Promotes the Differentiation of Myeloid-Derived Suppressor Cells in the Treatment of Psoriasis
title_short Acitretin Promotes the Differentiation of Myeloid-Derived Suppressor Cells in the Treatment of Psoriasis
title_sort acitretin promotes the differentiation of myeloid-derived suppressor cells in the treatment of psoriasis
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021725/
https://www.ncbi.nlm.nih.gov/pubmed/33834031
http://dx.doi.org/10.3389/fmed.2021.625130
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