Author(s):
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 ; Silva, José A. P. da ; Paiva, Artur
Date: 2023
Persistent ID: https://hdl.handle.net/10316/113268
Origin: Estudo Geral - Universidade de Coimbra
Subject(s): mesenchymal stromal cells (MSCs); mesenchymal stemcells; immunomodulatory potential; systemic sclerosis; T cells; T cell polarization; T cell activation; Treg; Th17; cellular therapy
Description
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, n = 6) and SSc patients (n = 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+, CD4+CD8+, CD4-CD8-, 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.
