Laranjeira Paula, Dos Santos Francisco, Salvador Maria João, Simões Irina N, Cardoso Carla M P, Silva Bárbara M, Henriques-Antunes Helena, Corte-Real Luísa, Couceiro Sofia, Monteiro Filipa, Santos Carolina, Santiago Tânia, da Silva José A P, Paiva Artur
Flow Cytometry Unit, Department of Clinical Pathology, Centro Hospitalar e Universitário de Coimbra, 3000-075 Coimbra, Portugal.
Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.
Biomedicines. 2023 Apr 30;11(5):1329. doi: 10.3390/biomedicines11051329.
Systemic sclerosis (SSc) is an immune-mediated disease wherein T cells are particularly implicated, presenting a poor prognosis and limited therapeutic options. Thus, mesenchymal-stem/stromal-cell (MSC)-based therapies can be of great benefit to SSc patients given their immunomodulatory, anti-fibrotic, and pro-angiogenic potential, which is associated with low toxicity. In this study, peripheral blood mononuclear cells from healthy individuals (HC, = 6) and SSc patients ( = 9) were co-cultured with MSCs in order to assess how MSCs affected the activation and polarization of 58 different T cell subsets, including Th1, Th17, and Treg. It was found that MSCs downregulated the activation of 26 out of the 41 T cell subsets identified within CD4, CD8, CD4CD8, CD4CD8, and γδ T cells in SSc patients (HC: 29/42) and affected the polarization of 13 out of 58 T cell subsets in SSc patients (HC: 22/64). Interestingly, SSc patients displayed some T cell subsets with an increased activation status and MSCs were able to downregulate all of them. This study provides a wide-ranging perspective of how MSCs affect T cells, including minor subsets. The ability to inhibit the activation and modulate the polarization of several T cell subsets, including those implicated in SSc's pathogenesis, further supports the potential of MSC-based therapies to regulate T cells in a disease whose onset/development may be due to immune system's malfunction.
系统性硬化症（SSc）是一种免疫介导的疾病，其中T细胞尤其受到牵连，预后较差且治疗选择有限。因此，基于间充质干/基质细胞（MSC）的疗法对SSc患者可能大有裨益，因为其具有免疫调节、抗纤维化和促血管生成的潜力，且毒性较低。在本研究中，将健康个体（HC，n = 6）和SSc患者（n = 9）的外周血单个核细胞与MSC共培养，以评估MSC如何影响58种不同T细胞亚群的激活和极化，包括Th1、Th17和Treg。研究发现，MSC下调了SSc患者（HC：29/42）中CD4、CD8、CD4CD8、CD4CD8和γδ T细胞内鉴定出的41个T细胞亚群中的26个的激活，并影响了SSc患者中58个T细胞亚群中的13个的极化（HC：22/64）。有趣的是，SSc患者表现出一些激活状态增加的T细胞亚群，而MSC能够下调所有这些亚群。本研究提供了关于MSC如何影响T细胞（包括次要亚群）的广泛观点。抑制多个T细胞亚群的激活并调节其极化的能力，包括那些与SSc发病机制有关的亚群，进一步支持了基于MSC的疗法在调节T细胞方面的潜力，这种疾病的发病/发展可能归因于免疫系统的功能失调。
