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Murine liver‐resident group 1 innate lymphoid cells regulate optimal priming of anti‐viral CD8 + T cells
Author(s) -
Krueger Peter D.,
Narayanan Sowmya,
Surette Fionna A.,
Brown Michael G.,
Sung SunSang J.,
Hahn Young S.
Publication year - 2017
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.3a0516-225r
Subject(s) - biology , innate lymphoid cell , immunology , cd8 , cd49b , priming (agriculture) , immune system , cytotoxic t cell , innate immune system , interleukin 21 , biochemistry , botany , germination , in vitro
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.