NK cells gain higher IFN-γ competence during terminal differentiation.

Autor: Luetke-Eversloh M; Innate Immunity, Deutsches Rheuma-Forschungszentrum, A Leibniz Institute, Berlin, Germany., Cicek BB, Siracusa F, Thom JT, Hamann A, Frischbutter S, Baumgrass R, Chang HD, Thiel A, Dong J, Romagnani C
Jazyk: angličtina
Zdroj: European journal of immunology [Eur J Immunol] 2014 Jul; Vol. 44 (7), pp. 2074-84. Date of Electronic Publication: 2014 May 19.
DOI: 10.1002/eji.201344072
Abstrakt: NK cells are the main cells of the innate immune system that produce IFN-γ, and they express this cytokine at early stages of maturation in response to cytokine stimulation. Conversely, acquisition of IFN-γ-competence in CD4(+) T helper cells requires a differentiation process from naïve toward type 1 (Th1) cells, which is associated with epigenetic remodeling at the IFNG locus. In the present study, we show that the ability of NK cells to produce IFN-γ in response to activating receptor (actR) engagement is gradually acquired during terminal differentiation and is accompanied by progressively higher NF-κB activation in response to actR triggering. Moreover, during the differentiation process NK cells gradually display increasing expression of IFNG and TBX21 (encoding T-bet) transcripts and demethylation at the IFNG promoter. This study provides new insights in the molecular mechanisms underlying NK-cell ability to express IFN-γ upon actR engagement. Thus, we propose that in order to efficiently produce IFN-γ in response to infected or transformed cells, NK cells gain Th1-like features, such as higher IFN-γ competence and epigenetic remodeling of the IFNG promoter, during their terminal differentiation.
(© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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