title: Unique and redundant functions of NKp46+ ILC3s in models of intestinal inflammation.
abstract: Group 3 ILCs (ILC3s) are innate sources of IL-22 and IL-17 and include lymphoid tissue-inducer (LTi)-like and NKp46(+) subsets. Both depend on RORγt and aryl hydrocarbon receptor, but NKp46(+)ILC3s also require Notch and T-bet for their development and are transcriptionally distinct. The extent to which these subsets have unique functions, especially in the context of T cell- and B cell-sufficient mice, remains largely unclear. To investigate the specific function of NKp46(+)ILC3s among other ILC3 subsets and T cells, we generated mice selectively lacking NKp46(+)ILC3s or all ILC3s and crossed them to T cell-deficient mice, thus maintaining B cells in all mice. In mice lacking T cells, NKp46(+)ILC3s were sufficient to promote inflammatory monocyte accumulation in the anti-CD40 innate colitis model through marked production of GM-CSF. In T cell-competent mice, lack of NKp46(+)ILCs had no impact on control of intestinal C. rodentium infection, whereas lack of all ILC3s partially impaired bacterial control. Thus, NKp46(+)ILC3s have a unique capacity to promote inflammation through GM-CSF-induced accumulation of inflammatory monocytes, but are superseded by LTi-like ILC3s and T cells in controlling intestinal bacterial infection.
authors.affiliation: Department of Pathology and Immunology and Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Christina
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Pathology and Immunology and Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Jacob S
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Pathology and Immunology and Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Susan
authors.initials: S
authors.lastname: Gilfillan
authors.affiliation: Department of Pathology and Immunology and Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Robinette
authors.affiliation: Department of Pathology and Immunology and Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Rodney D
authors.initials: RD
authors.lastname: Newberry
authors.affiliation: Department of Pathology and Immunology and Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Thaddeus S
authors.initials: TS
authors.lastname: Stappenbeck
authors.affiliation: Department of Nephrology, University Hospital Regensburg, 93042 Regensburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mack
authors.affiliation: Department of Pathology and Immunology and Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110 mcolonna@pathology.wustl.edu mcella@pathology.wustl.edu.
authors.forename: Marina
authors.initials: M
authors.lastname: Cella
authors.affiliation: Department of Pathology and Immunology and Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110 mcolonna@pathology.wustl.edu mcella@pathology.wustl.edu.
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000950:Antigens, Ly / Q000032:analysis / Q000502:physiology*; D019013:CD40 Antigens / Q000037:antagonists & inhibitors / Q000502:physiology; D044082:Citrobacter rodentium; D003092:Colitis / Q000276:immunology*; D004756:Enterobacteriaceae Infections / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D007113:Immunity, Innate; D007378:Interleukins / Q000502:physiology; D008214:Lymphocytes / Q000502:physiology*; D008297:Male; D051379:Mice; D009000:Monocytes / Q000502:physiology; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000032:analysis / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology; D000097043:Interleukin-22
chemical_list: D000950:Antigens, Ly; D019013:CD40 Antigens; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007378:Interleukins; D055627:Natural Cytotoxicity Triggering Receptor 1; D054390:Receptors, CCR2; D000097043:Interleukin-22; C515335:Ccr2 protein, mouse; C118384:Ncr1 protein, mouse