title: Interleukin-37 Enhances the Suppressive Activity of Naturally Occurring CD4+CD25+Regulatory T Cells.
abstract: Naturally occurring CD4+CD25+regulatory T cells (Tregs) are essential for the suppression of autoimmunity and can control the immune-mediated pathology during the early phase of sepsis. Our previous data showed that silencing interleukin-37 (IL-37) in human CD4+CD25+Tregs obviously reduced the suppressive activity of CD4+CD25+Tregs. Here, we found that rhIL-37 stimulation markedly enhanced the suppressive activity of CD4+CD25+Tregs isolated from naive C57BL/6 J mice in the absence or presence of lipopolysaccharide (LPS). Treatment with rhIL-37 could significantly upregulate the expression of cytotoxic T-lymphocyte-associated antigen (CTLA)-4 and forkhead/winged helix transcription factor p3 (Foxp3) on CD4+CD25+Tregs. Also, rhIL-37 stimulation promoted the production of transforming growth factor-β1 (TGF-β1) but not IL-10 in the supernatants of cultured CD4+CD25+Tregs. Pretreated CD4+CD25+Tregs with rhIL-37 in the presence or absence of LPS were cocultured with CD4+CD25-T cells, ratio of IL-4/interferon-γ in the supernatants obviously increased in IL-37-stimulated groups. In addition, early administration of IL-37 significantly improved the survival rate of septic mice induced by cecal ligation and puncture. Taken together, we concluded that rhIL-37 enhances the suppressive activity of CD4+CD25+Tregs and might be a potential immunomodulator for the treatment of septic complications.
authors.affiliation: Department of Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250101, P. R.China.|Trauma Research Center, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, P. R.China.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Wang
authors.affiliation: Trauma Research Center, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, P. R.China.
authors.forename: Ning
authors.initials: N
authors.lastname: Dong
authors.affiliation: Trauma Research Center, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, P. R.China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Trauma Research Center, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, P. R.China.
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Zhu
authors.affiliation: Department of Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250101, P. R.China.
authors.forename: Chun-Ting
authors.initials: CT
authors.lastname: Wang
authors.affiliation: Trauma Research Center, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, P. R.China.|State Key Laboratory of Kidney Disease, the Chinese PLA General Hospital, Beijing 100853, P. R.China.
authors.forename: Yong-Ming
authors.initials: YM
authors.lastname: Yao
mesh_terms: D000818:Animals; D060908:CTLA-4 Antigen / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D018805:Sepsis / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism / Q000502:physiology*
chemical_list: D060908:CTLA-4 Antigen; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C508587:IL37 protein, human; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D015847:Interleukin-4; D007371:Interferon-gamma