title: Expression of IL-37 contributes to the immunosuppressive property of human CD4+CD25+ regulatory T cells.
abstract: Interleukin-37 (IL-37) possesses the function of down-regulate systemic and local inflammation. It is unknown whether IL-37 is expressed in human regulatory T cells (Tregs) and its role in modulating the immune response of Tregs. In the present study, cell surface molecules and secretory cytokines were analyzed in order to determine the function of IL-37 in regulating inhibitory effect of human CD4(+)CD25(+)Tregs. Meanwhile, the effects of IL-37 on T cell differentiation and proliferation as co-culture of CD4(+)CD25(+)Treg/CD4(+)CD25(-)T cell were also investigated. It was showed that IL-37 was expressed in cytoplasm of CD4(+)CD25(+)Tregs, and the levels of IL-37 were gradually elevated with the enhanced activity of CD4(+)CD25(+)Tregs. Secretory cytokines such as transforming growth factor (TGF)-β and interleukin (IL)-10, and expressions of cell surface molecules, including forkhead/winged helix transcription factor p3 (FOXP3) and cytotoxic T-lymphocyte associated antigen (CTLA)-4, were significantly decreased when IL-37 gene was silenced by siRNA. Furthermore, down-regulation of IL-37 expression in human CD4(+)CD25(+)Tregs obviously promoted proliferation of co-cultured T cell and differentiation, together with observably enhancement of IL-2 formation. These results demonstrated that IL-37 might manifest as a critical protein involving in immunosuppression of human CD4(+)CD25(+)Tregs.
authors.affiliation: Trauma Research Center, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, China.|Department of Hepatobiliary Surgery, the 309th Hospital of Chinese PLA, Beijing 100091, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Shuai
authors.affiliation: Department of Hepatobiliary Surgery, the 309th Hospital of Chinese PLA, Beijing 100091, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wei-min
authors.affiliation: Department of Burns and Plastic Surgery, the 181st Hospital of Chinese PLA, Guilin 541002, China.
authors.forename: Ya-lin
authors.initials: YL
authors.lastname: Tong
authors.affiliation: Trauma Research Center, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, 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, China.
authors.forename: Zhi-yong
authors.initials: ZY
authors.lastname: Sheng
authors.affiliation: Trauma Research Center, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, China.
authors.forename: Yong-ming
authors.initials: YM
authors.lastname: Yao
mesh_terms: D015415:Biomarkers; D060908:CTLA-4 Antigen / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D018920:Coculture Techniques; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D056747:Immunomodulation / Q000235:genetics*; D007375:Interleukin-1 / Q000235:genetics* / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D015415:Biomarkers; D060908:CTLA-4 Antigen; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508609:IL10 protein, human; C508587:IL37 protein, human; D007375:Interleukin-1; D053645:Interleukin-2 Receptor alpha Subunit; D016212:Transforming Growth Factor beta; D016753:Interleukin-10