Wang Fangdi, Hou Ruixia, Li Junqin, Zhao Xincheng, Wang Qiang, Zhang Kaiming, Li Xinhua
Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, China.
Int J Stem Cells. 2022 May 30;15(2):155-163. doi: 10.15283/ijsc20210.
Mesenchymal stem cells (MSCs) have immunomodulatory function and participate in the pathogenesis of many immunoregulation-related diseases, including psoriasis. Previously, we found that MSCs from psoriatic lesions overexpress the proinflammatory microRNA, miR-155 and exhibit a decreased immunosuppressive capacity. But the origin of these aberrant characteristics is still not clear. To investigate whether inflammatory cytokines in serum and peripheral blood mononuclear cells (PBMCs) from psoriatic patients can regulate the expression patterns of immunoregulation-related cytokines and the immunoregulation function of MSCs.
Normal dermal mesenchymal stem cells (nDMSCs) were treated with serum or PBMCs derived from patients with psoriasis or healthy donors. Expression of miR-155 and immunoregulation-related genes in each MSCs were measured using real-time PCR or western-blot. Meanwhile, the immunosuppressive capacity of DMSCs was evaluated by its inhibitory ability on proliferation of activated PBMCs. Compared to control serum, psoriatic serum significantly increased the expression levels of miR-155 (27.19±2.40 vs. 3.51±1.19, p<0.001), while decreased TAB expression (0.28±0.04 vs. 0.72±0.20, p<0.01) in DMSCs. Expression levels of immunoregulation-related genes such as PGE, IL-10, and TLR4 were also markedly down-regulated following the psoriatic serum treatment. Those DMSCs treated with healthy serum could inhibit PBMC proliferation, while those psoriatic serum-treated DMSCs could not inhibit PBMC proliferation effectively.
Psoriatic serum up-regulate the expression of miR-155, down-regulate the expression of immunoregulation- related genes (PGE, IL-10, and TLR4) in DMSCs, and along with the inhibition of the immunosuppressive function of MSCs.
间充质干细胞（MSCs）具有免疫调节功能，参与包括银屑病在内的许多免疫调节相关疾病的发病机制。此前，我们发现银屑病皮损来源的MSCs过表达促炎微RNA miR-155，且免疫抑制能力下降。但这些异常特征的来源仍不清楚。旨在研究银屑病患者血清和外周血单个核细胞（PBMCs）中的炎性细胞因子是否能调节免疫调节相关细胞因子的表达模式及MSCs的免疫调节功能。
用银屑病患者或健康供体的血清或PBMCs处理正常真皮间充质干细胞（nDMSCs）。采用实时PCR或蛋白质印迹法检测各MSCs中miR-155和免疫调节相关基因的表达。同时，通过其对活化PBMCs增殖的抑制能力评估DMSCs的免疫抑制能力。与对照血清相比，银屑病血清显著增加了DMSCs中miR-155的表达水平（27.19±2.40对3.51±1.19，p<0.001），同时降低了TAB表达（0.28±0.04对0.72±0.20，p<0.01）。银屑病血清处理后，PGE、IL-10和TLR4等免疫调节相关基因的表达水平也明显下调。用健康血清处理的那些DMSCs可抑制PBMC增殖，而用银屑病血清处理的那些DMSCs不能有效抑制PBMC增殖。
银屑病血清上调DMSCs中miR-155的表达，下调免疫调节相关基因（PGE、IL-10和TLR4）的表达，并伴随抑制MSCs的免疫抑制功能。
