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Neuronal NLRC5 regulates MHC class I expression in Neuro‐2a cells and also during hippocampal development
Author(s) -
Li Ping,
Shen Yuqing,
Cui Pengfei,
Hu Yue,
Zhang Ying,
Miao Fengqin,
Zhang Aifeng,
Zhang Jianqiong
Publication year - 2020
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14876
Subject(s) - hippocampal formation , neuroscience , mhc class i , major histocompatibility complex , biology , mhc class ii , microbiology and biotechnology , immunology , immune system
Major histocompatibility Complex class I (MHC I) molecules are ubiquitously expressed, being found in most nucleated cells, where they are central mediators of both the adaptive and innate immune responses. Recent studies have shown that MHC I are also expressed in the developing brain where they participate in synapse elimination and plasticity. Up‐regulation of MHC I within the developing brain has been reported, however, the mechanism(s) regulating this developmental up‐regulation of neuronal MHC I remains unknown. Here, we show NLR family CARD domain containing 5 (NLRC5), a newly identified member of the NLR family, is widely expressed in hippocampal neurons, and the expression pattern of NLRC5 coincides with increased MHC I mRNA in the developing hippocampus. Using a luciferase assay in Neuro‐2a cells we demonstrate that NLRC5 can induce the activation of MHC I and this induction requires the W/S‐X‐Y motif. Further studies show that transcription factors regulatory factor X (RFX) and CREB1, which bind to X1 and X2 box, are crucial for NLRC5‐mediated induction. Moreover immunoprecipitation experiments reveal that NLRC5 interacts with RFX subunits RFX5 and RFXANK. Knockout of Nlrc5 dramatically impairs basal expression of MHC I in mouse hippocampus. Taken together, our findings identify NLRC5 as a key regulator of MHC I up‐regulation in the developing hippocampus and suggest an important role for NLRC5 in neurons.Cover Image for this issue: doi: 10.1111/jnc.14729 .