The intestinal epithelium, which segregates the highly stimulatory lumen from the underlying tissue, harbors one of the largest lymphocyte populations in the body, intestinal intraepithelial lymphocytes (IELs). IELs must balance tolerance, resistance, and tissue protection to maintain epithelial homeostasis and barrier integrity. This review discusses the ontogeny, environmental imprinting, T cell receptor (TCR) repertoire, and function of intestinal IELs. Despite distinct developmental pathways, IEL subsets share core traits including an epithelium-adapted profile, innate-like properties, cytotoxic potential, and limited TCR diversity. IELs also receive important developmental and functional cues through interactions with epithelial cells, microbiota, and dietary components. The restricted TCR diversity of IELs suggests that a limited set of intestinal antigens drives IEL responses, with potential functional consequences. Finally, IELs play a key role in promoting homeostatic immunity and epithelial barrier integrity but can become pathogenic upon dysregulation. Therefore, IELs represent intriguing but underexamined therapeutic targets for inflammatory diseases and cancer.Expected final online publication date for the Annual Review of Immunology, Volume 42 is April 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

中文翻译：

---

肠上皮内淋巴细胞

肠上皮将高度刺激的管腔与底层组织隔离开来，拥有体内最大的淋巴细胞群之一，即肠上皮内淋巴细胞 (IEL)。 IEL 必须平衡耐受性、抵抗力和组织保护，以维持上皮稳态和屏障完整性。这篇综述讨论了肠道 IEL 的个体发育、环境印记、T 细胞受体 (TCR) 库和功能。尽管发育途径不同，但 IEL 亚群具有共同的核心特征，包括上皮适应特征、先天性特性、细胞毒性潜力和有限的 TCR 多样性。 IEL 还通过与上皮细胞、微生物群和饮食成分的相互作用获得重要的发育和功能线索。 IEL 有限的 TCR 多样性表明，一组有限的肠道抗原驱动 IEL 反应，并具有潜在的功能后果。最后，IEL 在促进稳态免疫和上皮屏障完整性方面发挥着关键作用，但在调节失调时可能会致病。因此，IEL 代表了炎症性疾病和癌症的有趣但未经充分审查的治疗靶点。《免疫学年度评论》第 42 卷的预计最终在线出版日期为 2024 年 4 月。请参阅 http://www.annualreviews.org/page/journal/pubdates修订后的估计。