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Title: ICOS:ICOS-ligand interaction is required for type 2 innate lymphoid cell function, homeostasis, and induction of airway hyperreactivity.

Authors: Maazi, Hadi; Patel, Nisheel; Sankaranarayanan, Ishwarya; Suzuki, Yuzo; Rigas, Diamanda; Soroosh, Pejman; Freeman, Gordon J; Sharpe, Arlene H; Akbari, Omid

Published In Immunity, (2015 Mar 17)

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.

PubMed ID: 25769613 Exiting the NIEHS site

MeSH Terms: Animals; Asthma/genetics; Asthma/immunology*; Asthma/pathology; Female; Gene Expression Regulation; Homeostasis; Humans; Immunity, Innate; Inducible T-Cell Co-Stimulator Ligand/genetics; Inducible T-Cell Co-Stimulator Ligand/immunology*; Inducible T-Cell Co-Stimulator Protein/genetics; Inducible T-Cell Co-Stimulator Protein/immunology*; Interleukin-13/genetics; Interleukin-13/immunology; Interleukin-2/genetics; Interleukin-2/immunology; Interleukin-33; Interleukin-5/genetics; Interleukin-5/immunology; Interleukins/genetics; Interleukins/immunology; Lymphocytes/immunology*; Lymphocytes/pathology; Mice, Transgenic; Respiratory System/immunology; Respiratory System/pathology; STAT5 Transcription Factor/genetics; STAT5 Transcription Factor/immunology; Signal Transduction

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