染色质重塑基因Baf180/Bap180具有作为炎症抑制因子维持肠道固有免疫平衡的新功能

固有免疫是机体抵御环境微生物的第一道防线，既要快速启动足够的免疫反应清除入侵的病原微生物，又要防止过激的炎症反应伤害宿主本身。因此，了解如何维持机体免疫平衡是一个亟需解决的重要科学问题。继上一个基金委项目，我们利用果蝇的大规模遗传筛选发现染色体重塑相关基因bap180（人、鼠中为baf180/polybromo1）突变造成肠道感染敏感。本项目将首先验证bap180缺失果蝇感染后的高致死率不是由于病原菌的大量增殖，而是由于失控的炎症风暴；其次因为bap180的表达会受到感染的刺激，我们将进一步解析bap180是否受到固有免疫信号的调控，起到负反馈的作用；第三，我们将利用无菌果蝇，探讨存在共生菌的正常果蝇肠道中，bap180是如何监控机体的免疫平衡；最后，我们将借助构建好的肠上皮细胞敲除小鼠研究同源基因baf180在高等动物中的保守机制，以期通过该项目揭示一种新的维持肠道免疫动态平衡的新机理。

Initiation adequate immune reactions to eliminate pathogenic microbes, meanwhile avoidance hyper-inflammatory responses to reduce damages to host tissues are two sides of coin in immune system. Thus, how to keep immune regulation in balance becomes an urgent need to address the mechanism. By a genetic screening in the last NSFC, we identified Bap180 plays a protective role against bacterial infection in Drosophila gut. Here, we will try to confirm that whether Bap180 contributes to innate immune homeostasis in intestine as a feedback repressor to inhibit detrimental inflammation storm, rather than to limit the accretion of bacteria load. We also will investigate whether Bap80 is involved in the regulation of host-commensal flora interaction in the gut. Finally, taking advantage of knockout mice, we will study whether the mammalian homologue gene Baf180 owns the conserved function. In conclusion, our study will demonstrate an unexpected role for Bap180/Baf180 to maintain innate immune homeostasis in the gut.