Open AccessInterleukin-37 Enhances the Suppressive Activity of Naturally Occurring CD4+CD25+ Regulatory T Cells
Author(s) -
Dawei Wang,
Ning Dong,
Yao Wu,
Xiaomei Zhu,
Chunting Wang,
YongMing Yao
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep38955
Subject(s) - il 2 receptor , foxp3 , immune system , immunology , interleukin , cytotoxic t cell , cytokine , medicine , biology , t cell , biochemistry , in vitro
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.