Liu Panpan, Peng Cong, Chen Xiang, Wu Lisha, Yin Mingzhu, Li Jie, Qin Qunshi, Kuang Yehong, Zhu Wu
The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha, China.
Front Med (Lausanne). 2021 Mar 23;8:625130. doi: 10.3389/fmed.2021.625130. eCollection 2021.
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 CD11cMHC-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.
髓源性抑制细胞（MDSCs）数量增加与银屑病的发展有关。阿维A通过调节角质形成细胞的增殖和分化来治疗银屑病，但阿维A对免疫细胞的影响知之甚少。在此，我们报道银屑病患者外周血和皮肤病变中MDSCs和单核细胞源性MDSCs（M-MDSCs）增多。外周血中MDSCs和M-MDSCs的数量与疾病严重程度呈正相关。阿维A可减少银屑病患者外周血以及咪喹莫特诱导的银屑病样模型小鼠脾脏和皮肤病变中MDSCs和M-MDSCs的数量。此外，阿维A促进MDSCs向巨噬细胞分化，尤其是CD206 M2巨噬细胞和CD11cMHC-II树突状细胞。机制上，阿维A显著增加MDSCs中谷胱甘肽合成酶（GSS）的表达和谷胱甘肽（GSH）的积累。GSH合成的中断消除了阿维A对MDSCs分化的作用。阿维A通过激活细胞外信号调节激酶1/2来调节GSS表达。因此，我们的数据揭示了阿维A通过促进MDSCs分化对银屑病产生作用的一种新机制。
