IL-36通过自噬调控脓毒症状态下调节性T细胞免疫功能的作用及其机制

Sepsis is essentially an immunological dissonance provoked by acute insults. Regulatory T cells (Treg) play crucial roles in sepsis-induced immune dysfunction. Interleukin-36 (IL-36) is a newly discovered inflammatory cytokine of IL-1 family. The key role has been approved in various inflammatory diseases. However, its significance and potential mechanism underlying immunological dissonance during sepsis remains unclear. We recently found that IL-36 and IL-36R were positively expressed in mouse Tregs and IL-36 can induce autophagy. With both cell and animal experiments and clinical observation, the present project was conducted to investigate the effect of IL-36 on immune function of Tregs in the pathogenesis of sepsis. Meanwhile, it would be further illustrated that through AMPK/Beclin1 signaling activating the autophagy of Treg. This study might shed a fresh light on the immunological effect of IL-36 and its regulatory mechanism, which could contribute to developing a new way for immunomodulatory strategy in septic complications.

脓毒症的发生与免疫功能紊乱密切相关，而调节性T细胞(Treg)在脓毒症免疫功能障碍中发挥重要的作用。白细胞介素36(IL-36)是IL-1家族新近发现的细胞因子，在炎症性疾病中具有重要的免疫调节效应。目前，IL-36在脓毒症中对Treg细胞免疫功能的作用、意义及其调节机制尚未明确。我们前期研究发现IL-36和IL-36R在Treg细胞中表达，并且IL-36能激活自噬。本项目拟通过体内外实验和临床观察，以Treg细胞为研究对象，探讨脓毒症状态下IL-36的表达规律及其对Treg免疫功能的影响，并从自噬的角度探索其免疫效应机制；进一步揭示IL-36通过自噬影响Treg免疫功能；在此基础上，明确AMPK/Beclin1信号通路是IL-36激活自噬的潜在途径；本研究从新的角度阐述了脓毒症状态下IL-36与Treg细胞免疫功能紊乱的内在联系及其关键信号通路，为脓毒症的临床救治提供新的靶点。

脓毒症的发生与免疫功能紊乱密切相关，而调节性T细胞(Treg)在脓毒症免疫功能障碍中发挥重要的作用。白细胞介素36(IL-36)是IL-1家族新近发现的细胞因子，在炎症性疾病中具有重要的免疫调节效应。目前，IL-36在脓毒症中对Treg细胞免疫功能的作用、意义及其调节机制尚未明确。我们研究发现IL-36和IL-36R在Treg细胞中表达，并且IL-36能激活自噬。本项目拟通过体内外实验和临床观察，以Treg细胞为研究对象，探讨脓毒症状态下IL-36的表达规律及其对Treg免疫功能的影响，并从自噬的角度探索其免疫效应机制；进一步揭示IL-36通过自噬影响Treg免疫功能；在此基础上，明确Beclin1信号通路是IL-36激活自噬的潜在途径；本研究从新的角度阐述了脓毒症状态下IL-36与Treg细胞免疫功能紊乱的内在联系及其关键信号通路，为脓毒症的临床救治提供新的靶点。