Issue Cover (January 2020)

Front cover: MHC class I (MHC I) molecules are important components of the immune system. Recently MHC I have been reported to play important roles in brain development and synaptic plasticity. Although important functions and up‐regulated expression of MHC I in developing neurons have been reported, the mechanism that govern neuronal MHC I up‐regulation remains unknown. NLR family CARD domain containing 5 (NLRC5), a newly identified member of the NLR family, is widely expressed in hippocampal neurons. NLRC5 is observed toco‐localize with MHC I with highest levels of expression found in hippocampal neurons. Moreover, NLRC5 activates MHC I transcription in neuron‐like cell line and this activation requires a functional W/S‐X‐Y motif in the promoter region that can bind to the RFX complex, CREB1 and the NFY complex. We also find that NLRC5 cooperates with RFX subunits RFX5 and RFXANK to promote MHC I expressionin neurons. Furthermore, we observed a significant reduction of MHC I levels in the hippocampal tissue of Nlrc5‐knockout mice. Overall, we demonstrated that NLRC5 as a key regulator of MHC I upregulation in the developing hippocampus and suggests an important role for NLRC5 in neurons. Image content: The image shows that NLRC5 protein(green) co‐localizes with MHC class I molecules(red) in the hippocampal neurons of P8 C57BL6/J mice. NLRC5 was present both in the cytoplasm and within nuclei while the majority of MHC I was displayed on membrane. The image suggests that NLRC5 and MHC I are both expressed by hippocampal neurons.Read the full preface   ‘Neuronal NLRC5 regulates MHC class I expression in Neuro-2a cells and also during hippocampal development’ by P. Li, Y. Shen, P. Cui, Y. Hu, Y. Zhang, F. Miao, A. Zhang, J. Zhang ( J. Neurochem . 2020, vol. 152 (2), pp. 182–194) on doi: 10.1111/jnc.14876