CFHR2 Supplementation Mitigates Pathologies of Neuromyelitis Optica by Regulating Complement Activation by Wei Jiang & Pengyan He & Mao Lin & Chongyou Zhang & Li Xu & Huiming Xu & Haoyang Li & Fan Zhu & Wenjing Luo & Xuan Li & Guangyou Wang & Shengjun Wang & Changyong Tang & Jiani Wang & Yan Lin & Shanshan Yang instant download

CFHR2 Supplementation Mitigates Pathologies of Neuromyelitis Optica by Regulating Complement Activation by Wei Jiang & Pengyan He & Mao Lin & Chongyou Zhang & Li Xu & Huiming Xu & Haoyang Li & Fan Zhu & Wenjing Luo & Xuan Li & Guangyou Wang & Shengjun Wang & Changyong Tang & Jiani Wang & Yan Lin & Shanshan Yang instant download

Abstract31 Neuromyelitis Optica spectrum disorder (NMOSD) is a relapsing autoimmune disease primarily 32 affecting the optic nerves and spinal cord. While the pathogenesis of NMO involves Aquaporin-4 33 antibodies (AQP4-IgG) and complement-mediated damage, the specific roles of the complement 34 pathway remain to be fully elucidated. In this study, we found that complement factor H-related 35 protein 2 (CFHR2), a regulator that inhibits the complement C3 alternative pathway, was 36 significantly decreased in the serum of NMO patients and was negatively correlated with the 37 Expanded Disability Status Scale (EDSS) score. Furthermore, we observed a marked reduction 38 in CFHR2 expression in astrocytes in both in vitro and in vivo NMO models. Administration of 39 recombinant human CFHR2 protein or adeno-associated virus (AAV)-mediated overexpression 40 of CFHR2 in astrocytes significantly alleviated NMO-related lesions and motor deficits by 41 inhibiting inflammation in these models. Additionally, CFHR2-modified functionalized 42 exosomes demonstrated efficacy in improving NMO-related lesions and motor dysfunction, 43 offering a promising new therapeutic strategy for NMO.