title: ICOS:ICOS-ligand interaction is required for type 2 innate lymphoid cell function, homeostasis, and induction of airway hyperreactivity.
abstract: Allergic asthma is caused by Th2-cell-type cytokines in response to allergen exposure. Type 2 innate lymphoid cells (ILC2s) are a newly identified subset of immune cells that, along with Th2 cells, contribute to the pathogenesis of asthma by producing copious amounts of IL-5 and IL-13, which cause eosinophilia and airway hyperreactivity (AHR), a cardinal feature of asthma. ILC2s express ICOS, a T cell costimulatory molecule with a currently unknown function. Here we showed that a lack of ICOS on murine ILC2s and blocking the ICOS:ICOS-ligand interaction in human ILC2s reduced AHR and lung inflammation. ILC2s expressed both ICOS and ICOS-ligand, and the ICOS:ICOS-ligand interaction promoted cytokine production and survival in ILC2s through STAT5 signaling. Thus, ICOS:ICOS-ligand signaling pathway is critically involved in ILC2 function and homeostasis.
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, Los Angeles, California 90033, USA.
authors.forename: Hadi
authors.initials: H
authors.lastname: Maazi
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, Los Angeles, California 90033, USA.
authors.forename: Nisheel
authors.initials: N
authors.lastname: Patel
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, Los Angeles, California 90033, USA.
authors.forename: Ishwarya
authors.initials: I
authors.lastname: Sankaranarayanan
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, Los Angeles, California 90033, USA.
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, Los Angeles, California 90033, USA.
authors.forename: Diamanda
authors.initials: D
authors.lastname: Rigas
authors.affiliation: Janssen Research and Development, San Diego, California 92121, USA.
authors.forename: Pejman
authors.initials: P
authors.lastname: Soroosh
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Freeman
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Arlene H
authors.initials: AH
authors.lastname: Sharpe
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, Los Angeles, California 90033, USA. Electronic address: akbari@usc.edu.
authors.forename: Omid
authors.initials: O
authors.lastname: Akbari
mesh_terms: D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D007113:Immunity, Innate; D060945:Inducible T-Cell Co-Stimulator Ligand / Q000235:genetics / Q000276:immunology*; D060889:Inducible T-Cell Co-Stimulator Protein / Q000235:genetics / Q000276:immunology*; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D000067596:Interleukin-33; D015848:Interleukin-5 / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000235:genetics / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology* / Q000473:pathology; D008822:Mice, Transgenic; D012137:Respiratory System / Q000276:immunology / Q000473:pathology; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction
chemical_list: C556692:ICOS protein, human; C498514:ICOSLG protein, human; C556694:Icos protein, mouse; C400230:Icosl protein, mouse; C506535:Il33 protein, mouse; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D018793:Interleukin-13; D007376:Interleukin-2; D000067596:Interleukin-33; D015848:Interleukin-5; D007378:Interleukins; D050799:STAT5 Transcription Factor