Murine liver‐resident group 1 innate lymphoid cells regulate optimal priming of anti‐viral CD8+ T cells. Issue 1 (4th August 2016)

• Record Type: Journal Article
• Authors: Krueger, Peter D.; Narayanan, Sowmya; Surette, Fionna A.; Brown, Michael G.; Sung, Sun‐Sang J.; Hahn, Young S.
• Is Part Of: Journal of leukocyte biology. Volume 101:Issue 1(2017)
• Page Start: 329
• Page End: 338
• Publication Date: 2016-08-04
• Subjects: immunity -- viruses -- natural killer cells -- T lymphocytes; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.3A0516-225R
• Languages: English
• ISSNs: 0741-5400

Abstract

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. Abstract : Intersection of innate and adaptive immunity in viral infection and implications for vaccine design.