Yingfang LiuSun Yat-sen University, China
Title: The function and mechanism of IFP35 family proteins in promoting neuroinflammation during the development of multiple sclerosis
Multiple sclerosis (MS) is a chronic inflammation-mediated demyelination disease in the central nervous system (CNS). Damaged neurons without myelin protection cannot transmit signals properly, resulting in impaired motor and sensory functions in MS patients, which makes MS to be one of the leading causes of disability in young adults. The past decades of investigations revealed that excessive activation of T cells and microglia represents a hallmark of MS pathogenesis. However, the regulatory molecules overactivating these immune cells remain to be identified. Previously, we reported that extracellular IFP35 family proteins, including IFP35 and NMI, activated macrophages as proinflammatory molecules in the periphery, through TLR4 mediated proinflammatory signal pathway. In recent years, we have investigated their functions in the process of neuroinflammation during MS development.Clinical transcriptomic data analysis revealed that expression of IFP35 family proteins was up-regulated in patients with MS. Further studies found that IFP35/NMI activated dendritic cells and promoted naïve T cell differentiation into Th1 and Th17 cells. Gene knockout of either nmi or ifp35, or administration of neutralizing antibodies against IFP35 alleviated the immune cells’ infiltration and demyelination in the CNS, thus reducing the severity of experimental autoimmune encephalomyelitis. These findings revealed a new mechanism by which IFP35 family proteins promote the overactivation of both T cells and microglia, advancing our understanding of the pathogenesis of MS and suggesting a potential target for MS diagnosis and treatment.
Yingfang Liu has completed his PHD from Peking University, China, and trained as postdoctoral fellow in US. He is now a professor and the head of the Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, Sun Yat-Sen University, China.