IL-33 relieves nerve injury by mediating microglial polarization in neuromyelitis optica spectrum disorders via the IL-33/ST2 pathway

• Published in: IBRO neuroscience reports 2024-12, Vol.17, p.177-187
• Main Authors: Huang, Lu, Fu, Congcong, Liao, Sha, Long, Youming
• Format: Article
• Language: English
• Subjects: AQP4; IL-33; Microglia; NMOSD; ST2
• ISSN: 2667-2421; 2667-2421
• DOI: 10.1016/j.ibneur.2024.07.008

Interleukin-33 (IL-33) is a member of the interleukin-1 cytokine family. Its function in regulating microglial M1/M2 polarization in neuromyelitis optica spectrum disorder (NMOSD) is still unelucidated. To evaluate the role of IL-33 in NMOSD, we constructed NMOSD mice model by injecting purified serum IgG from AQP4-IgG seropositive NMOSD patients into experimental autoimmune encephalomyelitis (EAE) mice, and IL-33 was intraperitoneally injected into NMOSD mice 3 d before the model induction. We found that pretreatment of the NMOSD mice with IL-33 relieved brain neuron loss, and demyelination and improved the structure of axons, astrocytes, and mitochondria. In the neuronal and microglial coculture system, pretreatment with IL-33 in microglia alleviated NMOSD serum-induced inflammation and damaged morphology in cultured neurons. IL-33 transformed microglia to the M2 phenotype, and NMOSD serum promoted microglia to the M1 phenotype in cultured BV2 cells. Moreover, IL-33 influenced microglial polarity via the IL-33/ST2 pathway. IL-33 may be a novel insight useful for further developing NMOSD-targeted therapy and drug development. •NMOSD serum promoted microglia to the M1 phenotype.•IL-33 transformed microglia to M2 phenotype which was dependent on ST2.•IL-33 pretreatment decreased NeuN loss and demyelination and improved the structure of astrocytes, axons and mitochondria