title: Murine liver-resident group 1 innate lymphoid cells regulate optimal priming of anti-viral CD8+ T cells.
abstract: The liver contains 2 transcriptionally distinct group 1 ILC subsets: CD49a+ILC1s and CD49b+NK cells. However, little is known about how group 1 ILCs contribute to hepatic immune responses. Therefore, we characterized murine liver-resident group 1 ILCs and found that CD49a+ILC1s express high levels of the inhibitory receptor NKG2A and localize near DCs in perivascular spaces surrounding the portal triads. Upon hepatic viral infection, NKG2A signaling in group 1 ILCs, especially in CD49a+ILC1s, inhibits CXCL9 expression required for robust accumulation of IFN-γ+CD49b+NK cells. As a consequence, NKG2A-/-mice showed increased numbers of IFN-γ-producing NK cells that preferentially activate liver CD103+DCs, leading to the sustained proliferation of adoptively transferred, virus-specific CD8+T cells. Collectively, these data suggest that group 1 ILCs play a role in maintaining the liver as a tolerogenic site by limiting the recruitment of peripheral NK cells during the early phase of viral infection. Furthermore, our findings implicate that the inhibition of NKG2A signaling on group 1 ILCs may be a novel vaccine strategy to induce robust CD8+T cell responses against persistent liver pathogens.
authors: Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia, USA.|Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia, USA.
authors: Peter D
authors: PD
authors: Krueger
authors: Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia, USA.|Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia, USA.
authors: Sowmya
authors: S
authors: Narayanan
authors: Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia, USA.
authors: Fionna A
authors: FA
authors: Surette
authors: Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia, USA.|Department of Medicine, University of Virginia, Charlottesville, Virginia, USA; and.
authors: Michael G
authors: MG
authors: Brown
authors: Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia, USA.|Department of Medicine, University of Virginia, Charlottesville, Virginia, USA; and.|Center for Immunity, Inflammation and Regenerative Medicine, University of Virginia, Charlottesville, Virginia, USA.
authors: Sun-Sang J
authors: SJ
authors: Sung
authors: Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia, USA; ysh5e@virginia.edu.|Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia, USA.
authors: Young S
authors: YS
authors: Hahn
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000998:Antiviral Agents / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002452:Cell Count; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D054370:Chemokine CXCL9 / Q000096:biosynthesis; D002630:Chemotactic Factors / Q000494:pharmacology; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects; D039001:Integrin alpha Chains / Q000378:metabolism; D039423:Integrin alpha1 / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D008099:Liver / Q000166:cytology*; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects; D008297:Male; D051379:Mice; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000172:deficiency / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000998:Antiviral Agents; D054370:Chemokine CXCL9; D002630:Chemotactic Factors; D000939:Epitopes; D039001:Integrin alpha Chains; D039423:Integrin alpha1; D055654:NK Cell Lectin-Like Receptor Subfamily C; C091367:alpha E integrins; D007371:Interferon-gamma
keywords: T lymphocytes; immunity; natural killer cells; viruses