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CKIP-1 regulates the immunomodulatory function of mesenchymal stem cells.

Mol. Biol. Rep.2019 Aug;46(4):3991-3999. Epub 2019 Jun 05
Youdi He 1 , Jun-Feng Chen 2 , Yan-Mei Yang 2 , Xiao-Hui Huang 3 , Xiao-Hui Dong 3 , Hui-Xin Yang 2 , Jun-Kai Cao 4 , Xiao-Xia Jiang 5
Youdi He 1 , Jun-Feng Chen 2 , Yan-Mei Yang 2 , Xiao-Hui Huang 3 , Xiao-Hui Dong 3 , Hui-Xin Yang 2 , Jun-Kai Cao 4 , Xiao-Xia Jiang 5
+ et al

[No authors listed]

Author information
  • 1 Department of Neurology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People's Republic of China.
  • 2 Department of Stomatology, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, People's Republic of China.
  • 3 Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, 27 Taiping Road, Haidian District, Beijing, 100850, People's Republic of China.
  • 4 Department of Stomatology, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, People's Republic of China. caojk@hotmail.com.
  • 5 Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, 27 Taiping Road, Haidian District, Beijing, 100850, People's Republic of China. smilovjiang@163.com.

摘要


Mesenchymal stem cells (MSCs) are self-renewing multipotent cells with immunoregulatory function, which makes them attractive candidates for regenerative medicine. However, the detailed mechanisms of their immunomodulatory capacity are not fully characterized. Here, we found that casein kinase 2 interacting protein-1 (CKIP-1) expression was induced in the murine MSC cell line C3H/10T1/2 by LPS. Knockdown of CKIP-1 did not cause significant differences on the cell cycle or immunophenotype of MSCs. However, MSCs with CKIP-1 knockdown showed enhanced immunosuppressive capacity. and western blot analyses revealed that compared with the control group, MSCs with CKIP-1-knockdown exhibited higher IL-10 production and p38 MAPK phosphorylation following LPS treatment. Interestingly, the expression of CKIP-1 was decreased in MSCs following high glucose treatment. Furthermore, MSCs became more immunosuppressive after high glucose treatment, as shown by higher IL-10 production and enhanced inhibition of T cell proliferation. Collectively, our data reveal a novel role for CKIP-1 in regulating MSC-mediated immunomodulation, and indicate that MSCs become more immunosuppressive under high glucose conditions. These new insights may help in the development of future applications of MSCs.

KEYWORDS: CKIP-1, Immunoregulatory function, Mesenchymal stem cells