Regulation of Gut Innate Lymphoid Cells by Ahr

Project Summary/Abstract RORgt+ ILC3s are abundant in the intestinal mucosa and play critical roles in gut tissue homeostasis and host- microbiome interactions under the steady state, and also contribute to host immunity during infection and inflammation. As a fundamental element for normal development of the immune system, iron is important for the proliferation and activation of T cells, and participates in the complex interplays among host, commensals, and pathogens. Our preliminary data suggest that iron metabolism is important for ILC3 maintenance and function. Ahr together with other transcription factors regulate the transcription of CD71, a key iron transporter that is crucial for maintaining a functional ILC3 compartment in the gut. Based on the premise and our preliminary data, we hypothesize that iron metabolism regulated by the Ahr-CD71 axis is important for intestinal ILC3 maintenance and function. Specifically, we will investigate 1) the iron impact on ILC3 maintenance and function, 2) the regulation of CD71 expression by Ahr-mediated pathway in ILC3s, and 3) the functional role of Ahr-mediated CD71 pathway in ILC3s during infection. The study represents an emerging paradigm of immune metabolism and nutrition immunology in health and disease, Successful completion of proposed experiments will offer an opportunity to elucidate the Ahr-CD71 axis in ILC3s in the gut under the steady state and during infection, and shed new light on the profound effect of environmental impact on host immunity.