Controversial role of ILC3s in intestinal diseases: A novelty perspective on immunotherapy

ILC3s have been identified as crucial immune regulators that play a role in maintaining host homeostasis and modulating the antitumor response. Emerging evidence supports the idea that LTi cells play an important role in initiating lymphoid tissue development, while other ILC3s can promote host defense and orchestrate adaptive immunity, mainly through the secretion of specific cytokines and crosstalk with other immune cells or tissues. Additionally, dysregulation of ILC3-mediated overexpression of cytokines, changes in subset abundance, and conversion toward other ILC subsets are closely linked with the occurrence of tumors and inflammatory diseases. Regulation of ILC3 cytokines, ILC conversion and LTi-induced TLSs may be a novel strategy for treating tumors and intestinal or extraintestinal inflammatory diseases. Herein, we discuss the development of ILCs, the biology of ILC3s, ILC plasticity, the correlation of ILC3s and adaptive immunity, crosstalk with the intestinal microenvironment, controversial roles of ILC3s in intestinal diseases and potential applications for treatment.