小柯机器人

中国科学技术大学朱书等研究人员合作发现，Gasdermin D许可MHCII诱导来维持小肠的食物耐受性。相关论文于2023年6月15日在线发表于国际学术期刊《细胞》。

研究人员发现肠道上皮细胞（IEC）积累了一个不太被认可的GSDMD的13kD N端片段，该片段在对食物抗原的反应中被caspase-3/7切割。与30kD的GSDMD切割片段不同的是，IEC积累的GSDMD切割片段会转移到细胞核，诱导CIITA和MHCII分子的转录，进而诱导小肠上部的Tr1细胞。用caspase-3/7抑制剂治疗的小鼠、对caspase-3/7切割有抵抗力的GSDMD突变的小鼠、IEC中MHCII缺乏的小鼠和Tr1缺乏的小鼠都显示出食物耐受性表型的破坏。这项研究支持GSDMD的不同切割可被理解为控制小肠免疫与耐受的调节中心。

据介绍，IEC构成了宿主细胞和众多外来抗原之间的主要屏障；目前还不清楚IEC如何诱导对病原体的保护性免疫，同时保持对食物的免疫耐受。

附：英文原文

Title: Gasdermin D licenses MHCII induction to maintain food tolerance in small intestine

Author: Kaixin He, Tingting Wan, Decai Wang, Ji Hu, Tingyue Zhou, Wanyin Tao, Zheng Wei, Qiao Lu, Rongbin Zhou, Zhigang Tian, Richard A. Flavell, Shu Zhu

Issue&Volume: 2023-06-15

Abstract: The intestinal epithelial cells (IECs) constitute the primary barrier between hostcells and numerous foreign antigens; it is unclear how IECs induce the protectiveimmunity against pathogens while maintaining the immune tolerance to food. Here, wefound IECs accumulate a less recognized 13-kD N-terminal fragment of GSDMD that iscleaved by caspase-3/7 in response to dietary antigens. Unlike the 30-kD GSDMD cleavagefragment that executes pyroptosis, the IEC-accumulated GSDMD cleavage fragment translocatesto the nucleus and induces the transcription of CIITA and MHCII molecules, which inturn induces the Tr1 cells in upper small intestine. Mice treated with a caspase-3/7inhibitor, mice with GSDMD mutation resistant to caspase-3/7 cleavage, mice with MHCIIdeficiency in IECs, and mice with Tr1 deficiency all displayed a disrupted food tolerancephenotype. Our study supports that differential cleavage of GSDMD can be understoodas a regulatory hub controlling immunity versus tolerance in the small intestine.

DOI: 10.1016/j.cell.2023.05.027

Source: https://www.cell.com/cell/fulltext/S0092-8674(23)00577-9