| First Author | Ge Y | Year | 2020 |
| Journal | J Infect Dis | Volume | 222 |
| Issue | 9 | Pages | 1517-1530 |
| PubMed ID | 32421784 | Mgi Jnum | J:304905 |
| Mgi Id | MGI:6513712 | Doi | 10.1093/infdis/jiaa258 |
| Citation | Ge Y, et al. (2020) Effect of Interleukin-36beta on Activating Autophagy of CD4+CD25+ Regulatory T cells and Its Immune Regulation in Sepsis. J Infect Dis 222(9):1517-1530 |
| abstractText | BACKGROUND: CD4+CD25+ regulatory T cells (Tregs) play an essential role in sepsis-induced immunosuppression. How, the effects of interleukin 36 (IL-36) cytokines on CD4+CD25+ Tregs and their underlying mechanism(s) in sepsis remain unknown. METHODS: Our study was designed to investigate the impacts of IL-36 cytokines on murine CD4+CD25+ Tregs in presence of lipopolysaccharide (LPS) and in a mouse model of sepsis induced by cecal ligation and puncture (CLP). IL-36-activated autophagy was evaluated by autophagy markers, autophagosome formation, and autophagic flux. RESULTS: IL-36alpha, IL-36beta, and IL-36gamma were expressed in murine CD4+CD25+ Tregs. Stimulation of CD4+CD25+ Tregs with LPS markedly up-regulated the expression of these cytokines, particularly IL-36beta. IL-36beta strongly suppressed CD4+CD25+ Tregs under LPS stimulation and in septic mice challenged with CLP, resulting in the amplification of T-helper 1 response and the proliferation of effector T cells. Mechanistic studies revealed that IL-36beta triggered autophagy of CD4+CD25+ Tregs. These effects were significantly attenuated in the presence of the autophagy inhibitor 3-methyladenine or Beclin1 knockdown. In addition, early IL-36beta administration reduced the mortality rate in mice subjected to CLP. Depletion of CD4+CD25+ Tregs before the onset of sepsis obviously abrogated IL-36beta-mediated protection against sepsis. CONCLUSIONS: These findings suggest that IL-36beta diminishes the immunosuppressive activity of CD4+CD25+ Tregs by activating the autophagic process, thereby contributing to improvement of the host immune response and prognosis in sepsis. |
