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J Leukoc Biol. 2017 Jan;101(1):329-338. doi: 10.1189/jlb.3A0516-225R. Epub 2016 Aug 4.

Murine liver-resident group 1 innate lymphoid cells regulate optimal priming of anti-viral CD8+ T cells.

Author information

1
Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia, USA.
2
Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia, USA.
3
Department of Medicine, University of Virginia, Charlottesville, Virginia, USA; and.
4
Center for Immunity, Inflammation and Regenerative Medicine, University of Virginia, Charlottesville, Virginia, USA.
5
Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia, USA; ysh5e@virginia.edu.

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.

KEYWORDS:

T lymphocytes; immunity; natural killer cells; viruses

PMID:
27493244
DOI:
10.1189/jlb.3A0516-225R
[Indexed for MEDLINE]

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