Intraepithelial lymphocytes promote intestinal regeneration through CD160/HVEM signaling

IF 7.9 2区 医学 Q1 IMMUNOLOGY Mucosal Immunology Pub Date : 2024-04-01 DOI:10.1016/j.mucimm.2024.02.004
Jiaoyan Huang , Xin Zhang , Hongkai Xu , Liuhui Fu , Yuke Liu , Jie Zhao , Jida Huang , Zuodong Song , Mingzhao Zhu , Yang-Xin Fu , Ye-Guang Chen , Xiaohuan Guo
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Abstract

Chemotherapy and radiotherapy frequently lead to intestinal damage. The mechanisms governing the repair or regeneration of intestinal damage are still not fully elucidated. Intraepithelial lymphocytes (IELs) are the primary immune cells residing in the intestinal epithelial layer. However, whether IELs are involved in intestinal epithelial injury repair remains unclear. Here, we found that IELs rapidly infiltrated the intestinal crypt region and are crucial for the recovery of the intestinal epithelium post-chemotherapy. Interestingly, IELs predominantly promoted intestinal regeneration by modulating the proliferation of transit-amplifying (TA) cells. Mechanistically, the expression of CD160 on IELs allows for interaction with herpes virus entry mediator (HVEM) on the intestinal epithelium, thereby activating downstream nuclear factor kappa (NF-κB) signaling and further promoting intestinal regeneration. Deficiency in either CD160 or HVEM resulted in reduced proliferation of intestinal progenitor cells, impaired intestinal damage repair, and increased mortality following chemotherapy. Remarkably, the adoptive transfer of CD160-sufficient IELs rescued the Rag1 deficient mice from chemotherapy-induced intestinal inflammation. Overall, our study underscores the critical role of IELs in intestinal regeneration and highlights the potential applications of targeting the CD160-HVEM axis for managing intestinal adverse events post-chemotherapy and radiotherapy.

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上皮内淋巴细胞通过 CD160/HVEM 信号促进肠道再生
化疗和放疗经常导致肠道损伤。肠道损伤的修复或再生机制仍未完全阐明。上皮内淋巴细胞(IELs)是驻留在肠上皮细胞层的主要免疫细胞。然而,IELs 是否参与肠上皮损伤修复仍不清楚。在这里,我们发现 IELs 快速浸润肠隐窝区域,对化疗后肠上皮的恢复至关重要。有趣的是,IELs主要通过调节转运扩增(TA)细胞的增殖来促进肠道再生。从机理上讲,IELs上CD160的表达可与肠上皮的HVEM相互作用,从而激活下游NF-κB信号,进一步促进肠道再生。CD160或HVEM的缺乏会导致肠祖细胞增殖减少、肠损伤修复受损以及化疗后死亡率升高。值得注意的是,CD160充足的IELs被收养性转移能挽救Rag1缺乏的小鼠,使其免于化疗引起的肠道炎症。总之,我们的研究强调了IELs在肠道再生中的关键作用,并突出了靶向CD160-HVEM轴在控制化疗和放疗后肠道不良反应方面的潜在应用。
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来源期刊
Mucosal Immunology
Mucosal Immunology 医学-免疫学
CiteScore
16.60
自引率
3.80%
发文量
100
审稿时长
12 days
期刊介绍: Mucosal Immunology, the official publication of the Society of Mucosal Immunology (SMI), serves as a forum for both basic and clinical scientists to discuss immunity and inflammation involving mucosal tissues. It covers gastrointestinal, pulmonary, nasopharyngeal, oral, ocular, and genitourinary immunology through original research articles, scholarly reviews, commentaries, editorials, and letters. The journal gives equal consideration to basic, translational, and clinical studies and also serves as a primary communication channel for the SMI governing board and its members, featuring society news, meeting announcements, policy discussions, and job/training opportunities advertisements.
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