title: The TNF-family cytokine TL1A promotes allergic immunopathology through group 2 innate lymphoid cells.
abstract: The tumor necrosis factor (TNF)-family cytokine TL1A (TNFSF15) costimulates T cells and promotes diverse T cell-dependent models of autoimmune disease through its receptor DR3. TL1A polymorphisms also confer susceptibility to inflammatory bowel disease. Here, we find that allergic pathology driven by constitutive TL1A expression depends on interleukin-13 (IL-13), but not on T, NKT, mast cells, or commensal intestinal flora. Group 2 innate lymphoid cells (ILC2) express surface DR3 and produce IL-13 and other type 2 cytokines in response to TL1A. DR3 is required for ILC2 expansion and function in the setting of T cell-dependent and -independent models of allergic disease. By contrast, DR3-deficient ILC2 can still differentiate, expand, and produce IL-13 when stimulated by IL-25 or IL-33, and mediate expulsion of intestinal helminths. These data identify costimulation of ILC2 as a novel function of TL1A important for allergic lung disease, and suggest that TL1A may be a therapeutic target in these settings.
authors.affiliation: Immunoregulation Section, Autoimmunity Branch, NIAMS, NIH, Bethesda, Maryland, USA.
authors.forename: F
authors.initials: F
authors.lastname: Meylan
authors.affiliation: Immunoregulation Section, Autoimmunity Branch, NIAMS, NIH, Bethesda, Maryland, USA.
authors.forename: E T
authors.initials: ET
authors.lastname: Hawley
authors.affiliation: Immunopathogenesis Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, Maryland, USA.
authors.forename: L
authors.initials: L
authors.lastname: Barron
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: J L
authors.initials: JL
authors.lastname: Barlow
authors.affiliation: Immunoregulation Section, Autoimmunity Branch, NIAMS, NIH, Bethesda, Maryland, USA.
authors.forename: P
authors.initials: P
authors.lastname: Penumetcha
authors.affiliation: Immunoregulation Section, Autoimmunity Branch, NIAMS, NIH, Bethesda, Maryland, USA.
authors.forename: M
authors.initials: M
authors.lastname: Pelletier
authors.affiliation: Lymphocyte Cell Biology Section, NIAMS, Bethesda, Maryland, USA.
authors.forename: G
authors.initials: G
authors.lastname: Sciumè
authors.affiliation: Immunoregulation Section, Autoimmunity Branch, NIAMS, NIH, Bethesda, Maryland, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Richard
authors.affiliation: Immunoregulation Section, Autoimmunity Branch, NIAMS, NIH, Bethesda, Maryland, USA.
authors.forename: E T
authors.initials: ET
authors.lastname: Hayes
authors.affiliation: Genetic Disease Research Branch, NHGRI, NIH, Bethesda, Maryland, USA.
authors.forename: J
authors.initials: J
authors.lastname: Gomez-Rodriguez
authors.affiliation: Laboratory of Immunology, NIAID, NIH, Bethesda, Maryland, USA.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.affiliation: Laboratory of Immunology, NIAID, NIH, Bethesda, Maryland, USA.
authors.forename: W E
authors.initials: WE
authors.lastname: Paul
authors.affiliation: Immunopathogenesis Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, Maryland, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Wynn
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: A N J
authors.initials: AN
authors.lastname: McKenzie
authors.affiliation: Immunoregulation Section, Autoimmunity Branch, NIAMS, NIH, Bethesda, Maryland, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Siegel
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism*; D007113:Immunity, Innate; D018793:Interleukin-13 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D053219:Receptors, Tumor Necrosis Factor, Member 25 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15
chemical_list: D016207:Cytokines; D018793:Interleukin-13; D053219:Receptors, Tumor Necrosis Factor, Member 25; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15