%0 Journal Article
%T Semaphorin3C identified as mediator of neuroinflammation and microglia polarization after spinal cord injury.
%A Shen J
%A Gong L
%A Sun Y
%A Lin J
%A Hu W
%A Wei J
%A Miao X
%A Gao T
%A Suo J
%A Xu J
%A Chai Y
%A Bao B
%A Qian Y
%A Zheng X
%J iScience
%V 27
%N 5
%D 2024 May 17
%M 38638567
%F 6.107
%R 10.1016/j.isci.2024.109649
%X Excessive neuroinflammation after spinal cord injury (SCI) is a major hurdle during nerve repair. Although proinflammatory macrophage/microglia-mediated neuroinflammation plays important roles, the underlying mechanism that triggers neuroinflammation and aggravating factors remain unclear. The present study identified a proinflammatory role of semaphorin3C (SEMA3C) in immunoregulation after SCI. SEMA3C expression level peaked 7 days post-injury (dpi) and decreased by 14 dpi. In vivo and in vitro studies revealed that macrophages/microglia expressed SEMA3C in the local microenvironment, which induced neuroinflammation and conversion of proinflammatory macrophage/microglia. Mechanistic experiments revealed that RAGE/NF-κB was downstream target of SEMA3C. Inhibiting SEMA3C-mediated RAGE signaling considerably suppressed proinflammatory cytokine production, reversed polarization of macrophages/microglia shortly after SCI. In addition, inhibition of SEMA3C-mediated RAGE signaling suggested that the SEMA3C/RAGE axis is a feasible target to preserve axons from neuroinflammation. Taken together, our study provides the first experimental evidence of an immunoregulatory role for SEMA3C in SCI via an autocrine mechanism.