Innate lymphoid cells, IL-22 and ID2: the essentials for a healthy gut

▸ Guo X, Liang Y, Zhang Y, et al. Innate lymphoid cells control early colonization resistance against intestinal pathogens through ID2-dependent regulation of the microbiota. Immunity 2015;42:731–743.

The microbiota regulates the host immune response to mediate colonisation resistance against pathogens. However, a number of host genetic factors also play a role in an individual's susceptibility to pathogen infection. If and how these host genetic factors contribute to colonisation resistance against pathogens through shaping the microbiota is unclear. Studies have shown that interleukin 22 (IL-22) shapes the gut microbiota by contributing to protection or exacerbation of IBD or infections. Group 3 innate lymphoid cells (ILC3s) are the major producers of IL-22 in the naïve gut. The development of ILC3s is dependent upon the interaction of Notch, ID2 and RORγt. ID2 belongs to a family of transcription factors that inhibit the function of E protein transcription factors by preventing them binding to DNA. The role of the highly expressed ID2 in differentiated ILCs is unclear. In this study by Guo and colleagues, mice in which ID2 was deleted from differentiated ILC3s exhibited greatly impaired gut colonisation resistance against Citrobacter rodentium. Continuous ID2 expression was found to be required for the homeostasis and function of ILC3s. Employing gnotobiotic hosts revealed that the ID2-dependent early colonisation resistance was mediated by IL-22 regulation of the microbiota. Interaction between ID2 and E2A was shown to regulate the function of IL-22 production in ILCs through the AhR and IL-23R pathways. Collectively, the authors demonstrated that IL-22-producing ILC3s are essential for regulating the microbiota to mediate early colonisation resistance against intestinal pathogens. From a clinical standpoint, this study suggests that a combination of microbiota transplantation and immune molecule treatment may restore a stable microbial community to prevent intestinal pathogen colonisation in patients with recurrent gut infection. …