Human umbilical cord-derived mesenchymal stem cells ameliorate psoriasis-like dermatitis by suppressing IL-17-producing γδ T cells
Human umbilical cord-derived mesenchymal stem cells ameliorate psoriasis-like dermatitis by suppressing IL-17-producing γδ T cells
复制标题
人脐带间充质干细胞通过抑制产生 IL-17 的 γ T 细胞改善银屑病样皮炎
DOI：
10.1007/s00441-022-03616-x
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发表时间：
2022-03-26
影响因子：
3.6
通讯作者：
Shi, Yuling
中科院分区：
文献类型：
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作者：
Chen, Youdong;Hu, Yifan;Shi, Yuling
骨髓间充质干细胞（Mesenchymal stem cells，MSCs）具有良好的免疫调节作用，在治疗自身免疫性疾病方面显示出巨大的潜力。银屑病是一种慢性缓解性免疫相关疾病。有限的研究表明，骨髓间充质干细胞可能是一种有效的治疗银屑病的方法，其潜在的机制仍有待阐明。在我们目前的研究中，人脐带来源的间充质干细胞（hUC-MSCs）皮下注射到咪喹莫特（IMQ）诱导的银屑病样皮肤炎症的小鼠中，以探索这种细胞治疗的可行性。银屑病样皮炎的严重程度通过累积银屑病面积和严重程度指数评分以及皮肤组织切片的表皮厚度进行评价。流式细胞术分析用于检测皮肤引流淋巴结中的T辅助细胞、调节性T细胞和γ δ T细胞。采用实时定量聚合酶链反应和酶联免疫吸附试验检测银屑病相关细胞因子和趋化因子在小鼠背部皮损中的表达水平。我们发现，hUC-MSCs大大降低了IMQ诱导的银屑病样皮炎的严重程度，并抑制了炎症细胞反应。虽然尾静脉注射hUC-MSCs也有效，但由于肺栓塞，其与较高的死亡率相关。通过比较，皮下注射200万hUC-MSC被确定为最佳治疗策略。此外，我们发现hUC-MSCs可能通过抑制产生白细胞介素-17的γ δ T细胞来抑制皮肤炎症。总之，皮下注射hUC-MSCs可能是一种有前途的银屑病治疗方法。我们的研究结果为hUC-MSC治疗银屑病的基础机制提供了新的见解。
Mesenchymal stem cells (MSCs) have shown great potential in treating autoimmune diseases due to their immunomodulatory capability, which has been verified in both animal experiments and clinical trials. Psoriasis is a chronic and remitting immune-related disease. Limited studies have demonstrated that MSCs might be an effective therapeutic approach for managing psoriasis, whose underlying mechanism remains to be elucidated. In our present study, human umbilical cord-derived MSCs (hUC-MSCs) were subcutaneously injected into mice with imiquimod (IMQ)-induced psoriasis-like skin inflammation to explore the feasibility of this cellular therapy. The severity of psoriasis-like dermatitis was evaluated by cumulative psoriasis area and severity index score and epidermal thickness of skin tissue sections. Flow cytometric analysis was utilized to detect T helper cells, regulatory T cells, and gamma delta T cells in skin-draining lymph nodes. Real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay were used to assess the expression levels of psoriasisrelated cytokines and chemokines in mouse dorsal skin lesions. We discovered that hUC-MSCs drastically diminished the severity of IMQ-induced psoriasis-like dermatitis and suppressed inflammatory cell response. Although the tail vein injection of hUC-MSCs was also effective, it was correlated with higher mortality owing to pulmonary embolism. By comparison, subcutaneous injection with two million hUC-MSCs was identified to be the optimal therapeutic strategy. Furthermore, we uncovered that hUC-MSCs might repress skin inflammation probably through inhibiting interleukin-17-producing gamma delta T cells. In conclusion, subcutaneous administration of hUC-MSCs might be a promising therapeutic approach for psoriasis. Our findings provide novel insights into the underpinning mechanism of hUC-MSC treatment in the management of psoriasis.