NK cells require IL-28R for optimal in vivo activity

F. Souza-Fonseca-Guimaraes, D. Mittal, L. Martinet, C. Bruedigam, K. Takeda, Chris Andoniou, Mariapia Degli-Esposti, G.R. Hill, M.J. Smyth, Arabella Young

Research output: Contribution to journalArticlepeer-review

73 Citations (Scopus)

Abstract

Natural killer (NK) cells are naturally circulating innate lymphoid cells that protect against tumor initiation and metastasis and contribute to immunopathology during inflammation. The signals that prime NK cells are not completely understood, and, although the importance of IFN type I is well recognized, the role of type III IFN is comparatively very poorly studied. IL-28R-deficient mice were resistant to LPS and cecal ligation puncture-induced septic shock, and hallmark cytokines in these disease models were dysregulated in the absence of IL-28R. IL-28R-deficient mice were more sensitive to experimental tumor metastasis and carcinogen-induced tumor formation than WT mice, and additional blockade of interferon alpha/beta receptor 1 (IFNAR1), but not IFN-γ, further enhanced metastasis and tumor development. IL-28R-deficient mice were also more susceptible to growth of the NK cell-sensitive lymphoma, RMAs. Specific loss of IL-28R in NK cells transferred into lymphocyte-deficient mice resulted in reduced LPS-induced IFN-γ levels and enhanced tumor metastasis. Therefore, by using IL-28R - deficient mice, which are unable to signal type III IFN-λ, we demonstrate for the first time, to our knowledge, the ability of IFN-λ to directly regulate NK cell effector functions in vivo, alone and in the context of IFN-αβ. © 2015, National Academy of Sciences. All rights reserved.
Original languageEnglish
Pages (from-to)E2376-E2384
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number18
Early online date21 Apr 2015
DOIs
Publication statusPublished - 5 May 2015

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