+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Mesenchymal stem cells inhibit T cell activation by releasing TGF-β1 from TGF-β1/GARP complex

Mesenchymal stem cells inhibit T cell activation by releasing TGF-β1 from TGF-β1/GARP complex

Oncotarget 8(59): 99784-99800

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.

Please choose payment method:

(PDF emailed within 1 workday: $29.90)

Accession: 065310153

Download citation: RISBibTeXText

PMID: 29245940

Related references

Hepatic Stellate Cells Inhibit T Cells through Active TGF-β1 from a Cell Surface-Bound Latent TGF-β1/GARP Complex. Journal of Immunology 195(6): 2648-2656, 2015

Human liver mesenchymal stem/progenitor cells inhibit hepatic stellate cell activation: in vitro and in vivo evaluation. Stem Cell Research and Therapy 8(1): 131, 2017

Human Umbilical Cord Mesenchymal Stem Cells Inhibit T Follicular Helper Cell Expansion Through the Activation of iNOS in Lupus-Prone B6.MRL- Fas lpr Mice. Cell Transplantation 26(6): 1031-1042, 2017

Microvesicles released from human embryonic stem cell derived-mesenchymal stem cells inhibit proliferation of leukemia cells. Oncology Reports 38(2): 1013-1020, 2017

Mesenchymal stem cells inhibit complement activation by secreting factor H. Stem Cells and Development 19(11): 1803-1809, 2010

Mesenchymal stem cells inhibit Th17 cells differentiation via IFN-γ-mediated SOCS3 activation. Immunologic Research 61(3): 219-229, 2015

MiRNAs and piRNAs from bone marrow mesenchymal stem cell extracellular vesicles induce cell survival and inhibit cell differentiation of cord blood hematopoietic stem cells: a new insight in transplantation. Oncotarget 7(6): 6676-6692, 2016

T Lymphocyte Prestimulation Impairs in a Time-Dependent Manner the Capacity of Adipose Mesenchymal Stem Cells to Inhibit Proliferation: Role of Interferon γ, Poly I:C, and Tryptophan Metabolism in Restoring Adipose Mesenchymal Stem Cell Inhibitory Effect. Stem Cells and Development 24(18): 2158-2170, 2015

HGF and direct mesenchymal stem cells contact synergize to inhibit hepatic stellate cells activation through TLR4/NF-kB pathway. Plos one 7(8): E43408, 2012

Adipose-derived mesenchymal stem cells inhibit activation of hepatic stellate cells in vitro and ameliorate rat liver fibrosis in vivo. Journal of the Formosan Medical Association 114(2): 130-138, 2015

Mesenchymal stem cells deliver synthetic microRNA mimics to glioma cells and glioma stem cells and inhibit their cell migration and self-renewal. Oncotarget 4(2): 346-361, 2013

Bone marrow-derived mesenchymal stem cells maintain the resting phenotype of microglia and inhibit microglial activation. Plos one 8(12): E84116, 2013

Umbilical cord blood-derived mesenchymal stem cells inhibit, but adipose tissue-derived mesenchymal stem cells promote, glioblastoma multiforme proliferation. Stem Cells and Development 22(9): 1370-1386, 2013

Mesenchymal stem cells overexpressing IL-35 effectively inhibit CD4 + T cell function. Cellular Immunology 312: 61-66, 2017

Mesenchymal stem cells inhibit Th17 cell differentiation by IL-10 secretion. Experimental Hematology 40(9): 761-770, 2012