Mesenchymal stem cells inhibit T cell activation by releasing TGF-β1 from TGF-β1/GARP complex
نویسندگان
چکیده
Intervention with mesenchymal stem cells (MSCs) reveals a promising therapeutic tool to treat transplantation and autoimmune disease due to their immunoregulation capability. But the mechanisms of action are not fully investigated yet. Transforming growth factor-β1 (TGF-β1) exhibit multiple effects in migration, differentiation, and immunomodulation of MSCs. Glycoprotein A repetitions predominant (GARP) is an important marker of activated Treg (regulatory T cells). GARP binds latent TGF-β1 to regulate its activation, which is the indispensable step in Treg suppressing effector T cells. So far we don't know whether GARP present on MSCs and its association with MSCs function. Our study show that MSCs express GARP which binds latent TGF-β1 on their cell surface. We also found that TGF-β1+/- MSCs produce less TGF-β1 and exhibit reduced capacity in inhibiting T cells. When TGF-β1 signaling pathway was blocked, MSCs show decreased activity in inhibiting T cells. Importantly, silencing GARP expression distinctively damaged the capacity of MSCs to inhibit IFN-γ production. These findings indicated the expression of GARP on MSCs and its functionality in activating LAP, thus demonstrating GARP as a novel biomarker and new target to improve the therapeutic efficacy of MSCs.
منابع مشابه
TGF-Β1 Transduced Mesenchymal Stem Cells Have Profound Modulatory Effects on DCs and T Cells
Background: Mesenchymal stem cells (MSCs) and transforming growth factor-β1 (TGF-β1) molecules are well known for their immunomodulatory properties and their function in tissue regeneration and remodeling. Objectives: To evaluate the interaction of TGF-β1 engineered MSCs with T cells and dendritic cells (DCs) and their modulatory effect on the immune response. Methods: MSCs and DCs were generat...
متن کاملMesenchymal Stromal Cells Express GARP/LRRC32 on Their Surface: Effects on Their Biology and Immunomodulatory Capacity
Mesenchymal stromal cells (MSCs) represent a promising tool for therapy in regenerative medicine, transplantation, and autoimmune disease due to their trophic and immunomodulatory activities. However, we are still far from understanding the mechanisms of action of MSCs in these processes. Transforming growth factor (TGF)-β1 is a pleiotropic cytokine involved in MSC migration, differentiation, a...
متن کاملHuman Leukocyte Antigen-G Expression on Dendritic Cells Induced by Transforming Growth Factor-β1 and CD4+ T Cells Proliferation
Background: During antigen capture and processing, mature dendritic cells (DC) express large amounts of peptide-MHC complexes and accessory molecules on their surface. DC are antigen-presenting cells that have an important role in tolerance and autoimmunity. The transforming growth factor-beta1 (TGF-β1) cytokine has a regulatory role on the immune and non-immune cells. The aim of this study is ...
متن کاملTGF-β1 enhanced myocardial differentiation through inhibition of the Wnt/β-catenin pathway with rat BMSCs
Objective(s): To investigate and test the hypotheses that TGF-β1 enhanced myocardial differentiation through Wnt/β-catenin pathway with rat bone marrow mesenchymal stem cells (BMSCs).Materials and Methods: Lentiviral vectors carrying the TGF-β1 gene were transduced into rat BMSCs firstly. Then several kinds of experimental methods were u...
متن کاملRegulation of the expression of GARP/latent TGF-β1 complexes on mouse T cells and their role in regulatory T cell and Th17 differentiation.
GARP/LRRC32 was defined as a marker of activated human regulatory T cells (Tregs) that is responsible for surface localization of latent TGF-β1. We find that GARP and latent TGF-β1 are also found on mouse Tregs activated via TCR stimulation; however, in contrast to human Tregs, GARP is also expressed at a low level on resting Tregs. The expression of GARP can be upregulated on mouse Tregs by IL...
متن کامل