SOCS1 regulates the immune modulatory properties of mesenchymal stem cells by inhibiting nitric oxide production.
Mesenchymal stem cells (MSCs) have been shown to be highly immunosuppressive and have been employed to treat various immune disorders. However, the mechanisms underlying the immunosuppressive capacity of MSCs are not fully understood. We found the suppressor of cytokine signaling 1 (SOCS1) was induced in MSCs treated with inflammatory cytokines. Knockdown of SOCS1 did not bring much difference on the proliferation and differentiation properties of MSCs. However, MSCs with SOCS1 knockdown exhibited enhanced immunosuppressive capacity, showing as inhibiting T cell proliferation at extremely low ratio (MSC to T) in vitro, significantly promoting tumor growth and inhibiting delayed-type hypersensitivity response in vivo. We further demonstrated that SOCS1 inhibited the immunosuppressive capacity of MSCs by reducing inducible nitric oxide synthase (iNOS) expression. Additionally, we found the significantly lower SOCS1 expression and higher nitric oxide (NO) production in MSCs isolated from synovial fluid of rheumatoid arthritis patients. Collectively, our data revealed a novel role of SOCS1 in regulating the immune modulatory activities of MSCs.
Institute of Basic Medical Sciences, Beijing, China; Yanbian University, Yanji City, Jilin Province, China.
Lei
L
Zhang
Chinese PLA General Hospital, Beijing, China.
Rui-Jie
RJ
Dang
Institute of Basic Medical Sciences, Beijing, China.
Hong
H
Li
Chinese PLA General Hospital, Beijing, China.
Ping
P
Li
Chinese PLA General Hospital, Beijing, China.
Yan-Mei
YM
Yang
Institute of Basic Medical Sciences, Beijing, China.
Xi-Min
XM
Guo
Institute of Basic Medical Sciences, Beijing, China.
Xiao-Yan
XY
Wang
Yanbian University, Yanji City, Jilin Province, China.
Nan-Zhu
NZ
Fang
Institute of Basic Medical Sciences, Beijing, China.
Ning
N
Mao
Chinese PLA General Hospital, Beijing, China.
Ning
N
Wen
Institute of Basic Medical Sciences, Beijing, China.
Xiao-Xia
XX
Jiang
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation / Q000235:genetics; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000235:genetics / Q000378:metabolism*; D007165:Immunosuppression Therapy / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism
D016207:Cytokines; D007155:Immunologic Factors; D047908:Intracellular Signaling Peptides and Proteins; D050826:Suppressor of Cytokine Signaling Proteins; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II