1. LIGHT-HVEM Signaling in Innate Lymphoid Cell Subsets Protects Against Enteric Bacterial Infection.
- Author
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Seo GY, Shui JW, Takahashi D, Song C, Wang Q, Kim K, Mikulski Z, Chandra S, Giles DA, Zahner S, Kim PH, Cheroutre H, Colonna M, and Kronenberg M
- Subjects
- Adoptive Transfer, Adult, Animals, Cytokines metabolism, Disease Models, Animal, Enterobacteriaceae Infections pathology, Homeodomain Proteins genetics, Homeodomain Proteins metabolism, Host-Pathogen Interactions immunology, Host-Pathogen Interactions physiology, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Neuropeptides metabolism, Protein Transport, Receptors, CCR6 genetics, Receptors, CCR6 metabolism, Receptors, Tumor Necrosis Factor metabolism, Spleen microbiology, Spleen pathology, Yersinia enterocolitica pathogenicity, Enterobacteriaceae Infections prevention & control, Interferon-gamma metabolism, Lymphocytes immunology, Lymphocytes metabolism, Receptors, Tumor Necrosis Factor, Member 14 immunology, Receptors, Tumor Necrosis Factor, Member 14 metabolism, Signal Transduction, Tumor Necrosis Factor Ligand Superfamily Member 14 metabolism
- 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., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
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