Department of Pediatrics, University Hospital Wuerzburg, Wuerzburg, Germany.
Department of Oral and Craniomaxillofacial and Plastic Surgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Straße 62, 50924, Cologne, Germany.
Adv Rheumatol. 2023 Jul 31;63(1):37. doi: 10.1186/s42358-023-00317-z.
The importance of proinflammatory T-cells and their cytokine production in patients with autoimmune arthritis has been widely described. Due to their immunomodulatory properties, mesenchymal stem cells (MSCs) have come into focus as a potential therapeutic concept. The aim of this study was to investigate the influence of MSCs on the phenotype, cytokine profile, and functionality of naive and non-naive CD4 T-cells from healthy donors (HD) and patients with autoimmune arthritis under Th17-cytokine polarizing conditions in an explorative way using a transwell system prohibiting any cell-cell-contact.
Magnetically isolated naive and non-naive CD4 T-cells were stimulated under Th17-polarizing proinflammatory cytokine conditions in presence and absence of bone marrow derived mesenchymal stromal cells (MSCs). After an incubation period of 6 days, the proportions of the T-cell subpopulations TEMRA (CD45RACD27), memory (CD45RACD27), effector (CD45RACD27) and naive cells (CD45RACD27) were determined. Quantitative immunofluorescence intensity was used as a measure for IL-9, IL-17 and IFN-γ production in each subpopulation.
In isolated naive CD4 T-cells from HD and patients, MSCs suppressed the differentiation of naive towards an effector phenotype while memory and naive cells showed higher percentages in culture with MSCs. In patients, MSCs significantly decreased the proportion of IL-9 and IL-17 producing effector T-cells. MSCs also reduced IFN-γ production in the naive and memory phenotype from HD.
The results of the study indicate significant immunomodulatory properties of MSCs, as under Th17-polarizing conditions MSCs are still able to control T-cell differentiation and proinflammatory cytokine production in both HD and patients with autoimmune arthritis.
促炎性 T 细胞及其细胞因子的产生在自身免疫性关节炎患者中具有重要意义，这一点已得到广泛描述。间充质干细胞（MSCs）因其免疫调节特性而成为一种有潜力的治疗概念，引起了关注。本研究旨在采用一种禁止细胞间接触的 Transwell 系统，以探索性方式研究 MSCs 对来自健康供体（HD）和自身免疫性关节炎患者的幼稚和非幼稚 CD4 T 细胞表型、细胞因子谱和功能在 Th17 细胞因子极化条件下的影响。
在存在和不存在骨髓来源的间充质基质细胞（MSCs）的情况下，经磁分离的幼稚和非幼稚 CD4 T 细胞在 Th17 极化的促炎细胞因子条件下被刺激。孵育 6 天后，确定 T 细胞亚群 TEMRA（CD45RA CD27）、记忆（CD45RA CD27）、效应（CD45RA CD27）和幼稚细胞（CD45RA CD27）的比例。采用定量免疫荧光强度作为各亚群中 IL-9、IL-17 和 IFN-γ产生的测量指标。
在 HD 和患者的分离的幼稚 CD4 T 细胞中，MSCs 抑制幼稚细胞向效应表型分化，而记忆细胞和幼稚细胞在有 MSCs 的培养中显示出更高的比例。在患者中，MSCs 显著降低了产生效应 T 细胞的 IL-9 和 IL-17 的比例。MSCs 还降低了 HD 中幼稚和记忆表型的 IFN-γ产生。
研究结果表明 MSCs 具有显著的免疫调节特性，因为在 Th17 极化条件下，MSCs 仍然能够控制 HD 和自身免疫性关节炎患者的 T 细胞分化和促炎细胞因子的产生。
