期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 101, 期 1, 页码 329-338出版社
WILEY
DOI: 10.1189/jlb.3A0516-225R
关键词
immunity; viruses; natural killer cells; T lymphocytes
资金
- U.S. National Institutes of Health (NIH) National Institute of Diabetes and Digestive and Kidney Diseases [F30-DK104562, DK063222]
- NIH National Institute of Allergy and Infectious Diseases [U19-AI083024]
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-gamma(+)CD49b(+)NK cells. As a consequence, NKG2A(-/-) mice showed increased numbers of IFN-gamma-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.
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