IL-38通过PD-1/PD-L1通路调控脓毒症状态下调节性T细胞免疫效应及机制

国基评审专家1V1指导 中标率高出同行96.8%
结合最新热点,提供专业选题建议
深度指导申报书撰写,确保创新可行
指导项目中标800+,快速提高中标率
微信扫码咨询
中文摘要
IL-38是最新近发现的抑炎因子,在炎症和免疫性疾病中具有重要的免疫效应,但在脓毒症免疫功能障碍中的作用尚未报道。我们预实验发现,IL-38及其受体在调节性T细胞(Tregs)中表达,且在内毒素刺激后表达显著上调。同时,应用重组IL-38能显著增强脓毒症小鼠Tregs的免疫活性,提示IL-38在脓毒症Tregs免疫功能紊乱中具有重要的意义。本项目拟研究脓毒症状态下IL-38的表达规律及其对Tregs免疫功能的影响,来明确IL-38与Tregs功能紊乱的内在联系,并进一步阐明IL-38通过PD-1/PD-L1-AKT/mTORC1信号途径影响Tregs免疫活性。实验采用IL-38、PD-L1基因敲除小鼠模型,通过对该信号通路中的关键分子PD-L1和mTORC1表达进行干预,从不同层面探讨IL-38介导脓毒症时Tregs免疫效应及其关键信号通路,为脓毒症免疫调理治疗提供新思路。
英文摘要
As a newly-discovered anti-inflammatory cytokine, IL-38 plays a key role in the pathogenesis of various inflammatory and autoimmune diseases. Until now, significance of IL-38 in sepsis-induced dysfunction remains unclear. We recently found that IL-38 and its receptor were expressed in murine regulatory T cells (Tregs) and their expression were markedly up-regulated after LPS stimulation. Besides, recombinant IL-38 could obviously improve the activity of Tregs. With both cell and animal experiments and clinical observation, the present project will be conducted to investigate the effect of IL-38 on Treg activity during sepsis. Using cell or animal model of IL-38-knockdown or PD-L1-knockdown, we will explore the contribution of IL-38-mediated signaling (PD-1/PD-L1-AKT/mTORC1 pathway) in Tregs during sepsis. Taken together, our study will help to shed a fresh light on the immunological effect of IL-38 and its regulatory mechanisms, which develops a novel immunomodulatory strategy for the treatment of sepsis.
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
DOI:10.3389/fcell.2022.839248
发表时间:2022
期刊:Frontiers in cell and developmental biology
影响因子:5.5
作者:Ge Y;Huang M;Yao YM
通讯作者:Yao YM
DOI:--
发表时间:2021
期刊:Mediators of Inflammation
影响因子:--
作者:Yun Ge;Juan Chen;Yanting Hu;Xinyi Chen;Man Huang
通讯作者:Man Huang
Effect of Interleukin-36β on Activating Autophagy of CD4+CD25+ Regulatory T cells and Its Immune Regulation in Sepsis.
Interleukin-36β 对激活 CD4 CD25 调节性 T 细胞自噬及其脓毒症免疫调节的影响。
DOI:--
发表时间:2020
期刊:Journal of infectious diseases.
影响因子:--
作者:Yun Ge;Man Huang;Ning Dong;Yong-ming Yao
通讯作者:Yong-ming Yao
DOI:--
发表时间:2020
期刊:Frontiers in immunology.
影响因子:--
作者:Yun Ge;Man Huang;Yong-ming Yao
通讯作者:Yong-ming Yao
The effect and its regulatory mechanism of high mobility group box-1 protein on immune cells in inflammatory diseases.
高迁移率族box-1蛋白对炎症性疾病免疫细胞的作用及其调控机制
DOI:--
发表时间:2021
期刊:cells
影响因子:6
作者:Yun Ge;Man Huang;Yong-ming Yao
通讯作者:Yong-ming Yao
国内基金
海外基金
