The role of regulatory B cells (Bregs) in the Tregs-amplifying effect of Sirolimus.
Sirolimus can significantly amplify regulatory T cells (Tregs) in vivo and in vitro, but the specific mechanism of this has not been well documented. The role of regulatory B cells (Bregs) in the Tregs-amplifying effect of Sirolimus was investigated in peripheral blood mononuclear cells (PBMCs) in vitro in this study. The results showed that the percentages of both CD19+CD24+CD38+TGF-β1+ Bregs and CD19+CD24+CD38+IL-10+ Bregs to B cells were elevated by Sirolimus in PBMCs including B cells. Sirolimus significantly enhances the cytokine production of transforming growth factor-β1 (TGF-β1) and interleukin-10 (IL-10) in PBMCs with B cells, and the enhancement significantly decreased in PBMCs without B cells. The percentage of CD4+CD25+Foxp3+ Tregs to T cells was also elevated by Sirolimus in PBMCs including B cells. The elevation of Tregs percentage decreased in PBMCs without B cells and recovered when additional TGF-β1 and IL-10 were added. The amplification of Tregs by Sirolimus was partially inhibited when either TGF-β1 or IL-10 was neutralized, and it even disappeared when these two cytokines were both neutralized. These results indicate that Sirolimus can amplify Bregs and Tregs in PBMCs in vitro, and Bregs may be the why Sirolimus amplifies Tregs.
Department of Hepatobiliary, the 309th Hospital of Chinese People's Liberation Army, Beijing 100091, China.
Jiyong
J
Song
Organ Transplant Laboratory, the 309th Hospital of Chinese People's Liberation Army, Beijing 100091, China.
Li
L
Xiao
Department of Hepatobiliary, the 309th Hospital of Chinese People's Liberation Army, Beijing 100091, China.
Guosheng
G
Du
Organ Transplant Laboratory, the 309th Hospital of Chinese People's Liberation Army, Beijing 100091, China.
Yu
Y
Gao
Organ Transplant Laboratory, the 309th Hospital of Chinese People's Liberation Army, Beijing 100091, China.
Wen
W
Chen
Department of Hepatobiliary, the 309th Hospital of Chinese People's Liberation Army, Beijing 100091, China.
Shaozhen
S
Yang
Organ Transplant Laboratory, the 309th Hospital of Chinese People's Liberation Army, Beijing 100091, China.
Wenmei
W
Fan
Organ Transplant Institute, the 309th Hospital of Chinese People's Liberation Army, Beijing 100091, China. Electronic address: shibingyi@medmail.com.cn.
Bingyi
B
Shi
D060151:B-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D002450:Cell Communication; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D020123:Sirolimus
Breg; Immunosuppressive agent; Lymphocyte subset; Organ transplantation; Sirolimus; Treg