title: The Group 3 Innate Lymphoid Cell Defect in Aryl Hydrocarbon Receptor Deficient Mice Is Associated with T Cell Hyperactivation during Intestinal Infection.
abstract: 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.
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Sagie
authors.initials: S
authors.lastname: Wagage
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Gretchen
authors.initials: G
authors.lastname: Harms Pritchard
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Lucas
authors.initials: L
authors.lastname: Dawson
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Buza
authors.affiliation: Department of Medicine and Institute for Immunology, Perelman School of Medicine, Division of Gastroenterology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Gregory F
authors.initials: GF
authors.lastname: Sonnenberg
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Hunter
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency*; D007113:Immunity, Innate; D007378:Interleukins / Q000378:metabolism; D007410:Intestinal Diseases / Q000276:immunology / Q000378:metabolism / Q000469:parasitology*; D051379:Mice; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000172:deficiency*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014122:Toxoplasma / Q000276:immunology; D014124:Toxoplasmosis, Animal / Q000276:immunology* / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D007378:Interleukins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018336:Receptors, Aryl Hydrocarbon; D000097043:Interleukin-22; C484722:Ahr protein, mouse; C539901:Rorc protein, mouse