H3K4me3 Demethylase Kdm5a Is Required for NK Cell Activation by Associating with p50 to Suppress SOCS1.

Abstract:

:The H3K4me3 demethylase Kdm5a regulates gene transcription and is implicated in carcinogenesis. However, the role of Kdm5a in innate immune response remains poorly understood. Here, we demonstrate that Kdm5a deficiency impairs activation of natural killer (NK) cells, with decreased IFN-γ production. Accordingly, Kdm5a(-/-) mice are highly susceptible to Listeria monocytogenes (Lm) infection. During NK cell activation, loss of Kdm5a profoundly impairs phosphorylation and nuclear localization of STAT4, along with increased expression of suppressor of cytokine signaling 1 (SOCS1). Mechanistic studies reveal that Kdm5a associates with p50 and binds to the Socs1 promoter region in resting NK cells, leading to a substantial decrease in H3K4me3 modification and repressive chromatin configuration at the Socs1 promoter. Thus, Kdm5a is required for priming activation of NK cells by suppressing the suppressor, SOCS1. Our study provides insights into the epigenetic regulation of innate immune response of NK cells.

journal_name

Cell Rep

journal_title

Cell reports

authors

Zhao D,Zhang Q,Liu Y,Li X,Zhao K,Ding Y,Li Z,Shen Q,Wang C,Li N,Cao X

doi

10.1016/j.celrep.2016.03.035

subject

Has Abstract

pub_date

2016-04-12 00:00:00

pages

288-99

issue

2

issn

2211-1247

pii

S2211-1247(16)30291-1

journal_volume

15

pub_type

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