The Group 3 Innate Lymphoid Cell Defect in Aryl Hydrocarbon Receptor Deficient Mice Is Associated with T Cell Hyperactivation during Intestinal Infection

Intestinal infection with the intracellular parasite Toxoplasma gondii results in the translocation of commensal bacteria to peripheral organs and the development of a T cell response specific to the microbiota. In naïve mice, the recently described RORγt + group 3 innate lymphoid cell (ILC) population plays a critical role in promoting intestinal barrier function and limiting responses to gut-resident commensal bacteria. Given this role for group 3 ILCs, studies were performed to evaluate whether these cells might influence the immune response to mucosal infection with T . gondii . Phenotypic characterization of RORγt + ILCs in T . gondii infected mice revealed that this population decreased following challenge but the population that remained expressed costimulatory molecules and IL-22. One factor that influences the maintenance of RORγt + ILCs is the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, and Ahr -/- mice have a marked defect in the lamina propria group 3 ILC population. When Ahr -/- mice were challenged with T . gondii , they lost more weight than wild type controls. This disease course in Ahr -/- animals was associated with increased T cell responses to Toxoplasma antigen and crude commensal antigen preparations. Together, these data suggest that group 3 ILCs have a role in limiting T cell activation during intestinal infection.