Open AccessTelomerase governs immunomodulatory properties of mesenchymal stem cells by regulating FAS ligand expression
Author(s) -
Chen Chider,
Akiyama Kentaro,
Yamaza Takayoshi,
You YongOuk,
Xu Xingtian,
Li Bei,
Zhao Yimin,
Shi Songtao
Publication year - 2014
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.201303000
Subject(s) - telomerase , telomerase reverse transcriptase , fas ligand , mesenchymal stem cell , downregulation and upregulation , cancer research , context (archaeology) , microbiology and biotechnology , transfection , immune system , biology , stem cell , immunology , chemistry , cell culture , apoptosis , biochemistry , genetics , gene , paleontology , programmed cell death
Bone marrow mesenchymal stem cells ( BMMSC s) are capable of differentiating into multiple cell types and regulating immune cell response. However, the mechanisms that govern the immunomodulatory properties of BMMSC s are still not fully elucidated. Here we show that telomerase‐deficient BMMSC s lose their capacity to inhibit T cells and ameliorate the disease phenotype in systemic sclerosis mice. Restoration of telomerase activity by telomerase reverse transcriptase ( TERT ) transfection in TERT −/− BMMSC s rescues their immunomodulatory functions. Mechanistically, we reveal that TERT , combined with β‐catenin and BRG 1, serves as a transcriptional complex, which binds the FAS ligand ( FASL ) promoter to upregulate FASL expression, leading to an elevated immunomodulatory function. To test the translational value of these findings in the context of potential clinical therapy, we used aspirin treatment to upregulate telomerase activity in BMMSC s, and found a significant improvement in the immunomodulatory capacity of BMMSC s. Taken together, these findings identify a previously unrecognized role of TERT in improving the immunomodulatory capacity of BMMSC s, suggesting that aspirin treatment is a practical approach to significantly reduce cell dosage in BMMSC ‐based immunotherapies.