LRRC4 functions as a neuron-protective role in experimental autoimmune encephalomyelitis

作者：Yan Zhang, Di Li, Qiuming Zeng, Jianbo Feng, Haijuan Fu, Zhaohui Luo, Bo Xiao, Huan Yang, Minghua Wu · 发表于：Molecular Medicine · 年份：2021 · DOI：10.1186/s10020-021-00304-4 · 被引用次数：19 · 研究领域：Axon Guidance and Neuronal Signaling、Hereditary Neurological Disorders、Nerve injury and regeneration

Abstract Background Leucine rich repeat containing 4 (LRRC4), also known as netrin-G ligand-2 (NGL-2), belongs to the superfamily of LRR proteins and serves as a receptor for netrin-G2. LRRC4 regulates the formation of excitatory synapses and promotes axon differentiation. Mutations in LRRC4 occur in Autism Spectrum Disorder (ASD) and intellectual disability. Multiple sclerosis (MS) is a chronic neuroinflammatory disease with spinal cords demyelination and neurodegeneration. Here, we sought to investigate whether LRRC4 is involved in spinal cords neuron-associated diseases. Methods LRRC4 was detected in the CNS of experimental autoimmune encephalomyelitis (EAE) mice by the use of real-time PCR and western blotting. LRRC4 −/− mice were created and immunized with myelin oligodendrocyte glycoprotein peptide (MOG) 35–55 . Pathological changes in spinal cords of LRRC4 −/− and WT mice 15 days after immunization were examined by using hematoxylin and eosin (H&E), Luxol Fast Blue (LFB) staining and immunohistochemistry. The number of Th1/Th2/Th17/Treg cells in spleens and blood were measured with flow cytometry. Differential gene expression in the spinal cords from WT and LRRC4 −/− mice was analyzed by using RNA sequencing (RNA-seq). Adeno-associated virus (AAV) vectors were used to overexpress LRRC4 (AAV-LRRC4) and were injected into EAE mice to assess the therapeutic effect of AAV-LRRC4 ectopic expression on EAE. Results We report that LRRC4 is mainly expressed in neuron of spi...