title: Hypothesis: human umbilical cord blood-derived stromal cells regulate the Foxp3 expression of regulatory T cells through the TGF-β1/Smad3 pathway.
abstract: Despite the improvements in transplant immunology and clinical and supportive care, graft-versus-host disease (GVHD) is still among the most common causes of overall mortality and morbidity after allogeneic hematopoietic cell transplantation. The development and severity of GVHD are strongly related with post-transplant outcomes. New strategies should be explored to overcome GVHD. Regulatory T cells (Treg cells), as dedicated suppressors of diverse immune responses and inflammation and important gatekeepers of immune homeostasis, contribute to the prevention of graft rejection and induce transplantation tolerance. Foxp3, a transcription factor, is predominantly expressed in Treg cells and is a master regulator of the development and function of Treg cells. Foxp3 mutations and Foxp3 deficiency lead to lethal autoimmune lymphoproliferative disease, which results from a defect in Treg cells. TGF-β1 is required to maintain Foxp3 expression in Treg cells. We isolated a novel population from among CD34(+) cells in our laboratory, referred to as human umbilical cord blood-derived stromal cells (hUCBDSCs), which exert an immunosuppressive effect and can notably increase Foxp3 expression in Treg cells. Our previous study also revealed that hUCBDSCs constantly secrete TGF-β1. Based on the literature searchings and our experimental findings, we hypothesize that hUCBDSCs, which secrete a high level of TGF-β1, modulate the Foxp3 expression of Treg cells through the TGF-β1/Smad3 pathway to regulate GVHD.
authors.affiliation: Department of Hematology, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, People's Republic of China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.forename: Xing-Hua
authors.initials: XH
authors.lastname: Chen
mesh_terms: D005312:Fetal Blood / Q000166:cytology*; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005786:Gene Expression Regulation; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology; D006801:Humans; D008962:Models, Theoretical; D015398:Signal Transduction; D051900:Smad3 Protein / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1