The gastrointestinal tract is an immunologically rich organ, containing complex cell networks and dense lymphoid structures that safeguard this large absorptive barrier from pathogens, contribute to tissue physiology and support mucosal healing. Simultaneously, the immune system must remain tolerant to innocuous dietary antigens and trillions of normally beneficial microorganisms colonizing the intestine. Indeed, a dysfunctional immune response in the intestine underlies the pathogenesis of numerous local and systemic diseases, including inflammatory bowel disease, food allergy, chronic enteric infections or cancers. Here, we discuss group 3 innate lymphoid cells (ILC3s), which have emerged as orchestrators of tissue physiology, immunity, inflammation, tolerance and malignancy in the gastrointestinal tract. ILC3s are abundant in the developing and healthy intestine but their numbers or function are altered during chronic disease and cancer. The latest studies provide new insights into the mechanisms by which ILC3s fundamentally shape intestinal homeostasis or disease pathophysiology, and often this functional dichotomy depends on context and complex interactions with other cell types or microorganisms. Finally, we consider how this knowledge could be harnessed to improve current treatments or provoke new opportunities for therapeutic intervention to promote gut health.

胃肠道是一个免疫丰富的器官，包含复杂的细胞网络和密集的淋巴结构，可保护这一巨大的吸收屏障免受病原体侵害，有助于组织生理学并支持粘膜愈合。同时，免疫系统必须对无害的饮食抗原和肠道内数万亿正常有益的微生物保持耐受性。事实上，肠道免疫反应功能失调是许多局部和全身疾病的发病机制，包括炎症性肠病、食物过敏、慢性肠道感染或癌症。在这里，我们讨论第 3 组先天淋巴细胞 (ILC3)，它们已成为胃肠道组织生理学、免疫、炎症、耐受性和恶性肿瘤的协调者。ILC3 在发育中和健康的肠道中含量丰富，但它们的数量或功能在慢性疾病和癌症期间会发生改变。最新的研究为 ILC3 从根本上塑造肠道稳态或疾病病理生理学的机制提供了新的见解，而且这种功能二分法通常取决于环境以及与其他细胞类型或微生物的复杂相互作用。最后，我们考虑如何利用这些知识来改进当前的治疗方法或为治疗干预提供新的机会以促进肠道健康。