2. Academic Validation
  3. LIGHT-HVEM Signaling in Innate Lymphoid Cell Subsets Protects Against Enteric Bacterial Infection

LIGHT-HVEM Signaling in Innate Lymphoid Cell Subsets Protects Against Enteric Bacterial Infection

  • Cell Host Microbe. 2018 Aug 8;24(2):249-260.e4. doi: 10.1016/j.chom.2018.07.008.
Goo-Young Seo 1,  Jr-Wen Shui 2,  Daisuke Takahashi 2,  Christina Song 3,  Qingyang Wang 2,  Kenneth Kim 4,  Zbigniew Mikulski 5,  Shilpi Chandra 2,  Daniel A Giles 2,  Sonja Zahner 2,  Pyeung-Hyeun Kim 6,  Hilde Cheroutre 2,  Marco Colonna 3,  Mitchell Kronenberg 7
Affiliations

Affiliations

  • 1 Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA; Department of Molecular Bioscience, School of Biomedical Science and Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon 24341, Republic of Korea.
  • 2 Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
  • 3 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • 4 Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
  • 5 Microscopy and Histology Core, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
  • 6 Department of Molecular Bioscience, School of Biomedical Science and Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon 24341, Republic of Korea.
  • 7 Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA; Division of Biology, University of California San Diego, La Jolla, CA 92037, USA. Electronic address: mitch@lji.org.
PMID: 30092201 DOI: 10.1016/j.chom.2018.07.008
Abstract

Innate lymphoid cells (ILCs) are important regulators of early Infection at mucosal barriers. ILCs are divided into three groups based on expression profiles, and are activated by cytokines and neuropeptides. Yet, it remains unknown if ILCs integrate Other signals in providing protection. We show that signaling through herpes virus entry mediator (HVEM), a member of the tumor necrosis factor (TNF) receptor superfamily, in ILC3 is important for host defense against oral Infection with the Bacterial pathogen Yersinia enterocolitica. HVEM stimulates protective interferon-γ (IFN-γ) secretion from ILCs, and mice with HVEM-deficient ILC3 exhibit reduced IFN-γ production, higher Bacterial burdens and increased mortality. In addition, IFN-γ production is critical as adoptive transfer of wild-type but not IFN-γ-deficient ILC3 can restore protection to mice lacking ILCs. We identify the TNF Superfamily member, LIGHT, as the ligand inducing HVEM signals in ILCs. Thus HVEM signaling mediated by LIGHT plays a critical role in regulating ILC3-derived IFN-γ production for protection following Infection. VIDEO ABSTRACT.

Keywords

CCR6; HVEM; IFN-γ; LIGHT; Yersinia enterocolitica; ileum; infection; innate lymphoid cells.

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