Location: Diet, Genomics and Immunology LaboratoryTitle: Aryl hydrocarbon receptor signaling cell intrinsically inhibits intestinal group 2 innate lymphoid cell function
|LI, SHIYANG - University Of Florida|
|BOSTICK, JOHN - University Of Florida|
|YE, JIAN - University Of Florida|
|QIU, JU - Shanghai Institutes For Biological Sciences|
|ZHANG, BIN - University Of Florida|
|AVRAM, DORINA - University Of Florida|
|ZHOU, LIANG - University Of Florida|
Submitted to: Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/20/2018
Publication Date: 11/13/2018
Citation: Li, S., Bostick, J.W., Ye, J., Qiu, J., Zhang, B., Urban Jr, J.F., Avram, D., Zhou, L. 2018. Aryl hydrocarbon receptor signaling cell intrinsically inhibits intestinal group 2 innate lymphoid cell function. Immunity. 49(5):915-928,e5. https://doi.org/10.1016/j.immuni.2018.09.015.
Interpretive Summary: Natural plant derived compounds called flavonoids can regulate the function of many cells including those of the immune system. Some of these plant compounds work through a cell surface receptor molecule called the aryl hydrocarbon receptor (Ahr) to activate genes that regulate cell function. Recent studies show that Ahr can regulate innate lymphoid cells (ILCs) that are some of the first immune cells to respond to infection at mucosal surfaces in the intestine. When ILCs are not properly regulated to turn on and off at appropriate times in the immune response, they can also enhance inflammation that has negative effects on health. This study showed that Ahr was expressed at the highest levels by a subset of ILCs (ILC2) that help to control parasitic worm infections in the intestine of man and livestock. Activation of the Ahr suppresses ILC2 differentiation and function, but it promotes activation of ILC3 which are cells that are important in control of bacterial infection in the intestine. Thus, dietary compounds can regulate a a critical balance between ILCs important in generating the appropriate immune response to various pathogenic infections. This information is important to the pharmaceutical industry in their quest to find regulators of immunity and inflammation, both in humans and livestock, in order to better improve health and the appropriate response to infection. It is also important in demonstrating that proper nutrition can improve healthy outcomes.
Technical Abstract: Innate lymphoid cells (ILCs) are important for mucosal immunity. The intestine harbors all ILC subsets; however, how these cells orchestrate each other to achieve immune homeostasis and to mount appropriate immunity during infection remains elusive. Here, we show that the gut adaptation of the aryl hydrocarbon receptor (Ahr) expression is a key regulatory mode for the host to keep the ILC balance. Among ILCs, Ahr is most highly expressed by gut ILC2 in a positive feedback manner with unique chromatin remodeling features at the Ahr gene locus. Ahr suppresses ILC2 differentiation and function, specifically through dampening Gfi1-mediated ST2 expression in ILC2. Ablation of Ahr enhances anti-helminth immunity in the gut, while genetic or pharmacological activation of Ahr suppresses ILC2, but enhances ILC3 to protect the host from Citrobacter rodentium infection. Thus, the host regulates the gut ILC2-ILC3 balance by engaging the Ahr pathway to mount appropriate immunity against various pathogens.