Abstract
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.
Highlights
mesenchymal stem cells (MSCs) have the potential to effectively treat a wide range of diseases
We found Transforming growth factor-β1 (TGF-β1)+/− MSCs present reduced T cell inhibitory activity (Figure 1A), indicating that TGF-β1 is necessary for MSCs to inhibit T cells
We found significant increase of FoxP3 expression in T cells co-cultured in the presence of WT MSCs (Figure 1B)
Summary
MSCs have the potential to effectively treat a wide range of diseases. MSCs are among the first stem cells to be applied into clinical practice [1, 2]. MSCs have immunoregulation capability by both inhibiting the maturation/differentiation of dendritic cells and by suppressing the activation and/or function of T, B and NK cells. It is certain that we need to find the better characterization of MSCs and better understanding of of MSCs biology. TGF-β1 plays critical roles in many physiological and pathological conditions, including cell differentiation and apoptosis, inflammation regulation and tissue repair. TGF-β1 is produced as pro-TGF-β1 precursor in cells. Pro-TGF-β1 is cleaved into two fragments [3, 4]
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