title: IL-23 activates innate lymphoid cells to promote neonatal intestinal pathology.
abstract: Interleukin-23 (IL-23) responsive group 3 innate lymphoid cells (ILC3s) have been implicated in immune homeostasis and pathogenesis in the adult, but little is known about their roles in the newborn. Here we show that IL-23 promotes conversion of embryonic intestinal Lin(-)IL-23R(+)Thy1(+) cells into IL-22-producing Thy1(+)Sca-1(hi) ILC3s in vitro. Gut-specific expression of IL-23 also activated and expanded Thy1(+)Sca-1(hi) ILC3s, which produced IL-22, IL-17, interferon gamma (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF) and were distinct from canonical CD4(+) lymphoid tissue inducer (LTi) cells. These ILC3s accumulated under the epithelium in intercellular adhesion molecule (ICAM)-1-positive cell aggregates together with neutrophils that disrupted the epithelium, leading to the formation of discrete intestinal erosions, bleeding, and neonatal death. Genetic and antibody depletion of ILC3s rescued the mice from neonatal death. Antibiotic treatment of pregnant mothers and offspring prolonged survival of IL-23 transgenic mice, suggesting a role for the commensal flora on ILC3-induced pathogenesis. Our results reveal a novel role for the IL-23-ILC3s axis in the pathogenesis of neonatal intestinal inflammation.
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Lili
authors.initials: L
authors.lastname: Chen
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Zhengxiang
authors.initials: Z
authors.lastname: He
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Slinger
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Gerold
authors.initials: G
authors.lastname: Bongers
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Taciana L S
authors.initials: TLS
authors.lastname: Lapenda
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Pacer
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Jiao
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Monique F
authors.initials: MF
authors.lastname: Beltrao
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Soto
authors.affiliation: Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Noam
authors.initials: N
authors.lastname: Harpaz
authors.affiliation: Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Gordon
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.|Department of Nephrology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Jordi C
authors.initials: JC
authors.lastname: Ochando
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, WA 98101, USA.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Oukka
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Alina Cornelia
authors.initials: AC
authors.lastname: Iuga
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48105, USA.|Section of Pathology and Laboratory Medicine, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI 48105, USA.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Chensue
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Julie Magarian
authors.initials: JM
authors.lastname: Blander
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Glaucia C
authors.initials: GC
authors.lastname: Furtado
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Lira
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D016130:Immunophenotyping; D053759:Interleukin-23 / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D007422:Intestines / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010539:Permeability; D010641:Phenotype
chemical_list: D000954:Antigens, Surface; D016207:Cytokines; D053759:Interleukin-23