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<p>Microglial polarization toward M1/M2 phenotypes is crucial in modulating neuroinflammation following spinal cord injury (SCI). This study aimed to investigate the role of interferon alpha-inducible protein 27-like 2A (<i>Ifi27l2a</i>) in regulating microglial polarization in SCI. The expression of <i>Ifi27l2a</i> were analyzed using single-cell RNA sequencing. C57BL/6 mice that underwent SCI were pretreated with adeno-associated virus (AAV) carrying sh-Ifi27l2a. In vitro, BV-2 cells were transfected with si-Ifi27l2a and stimulated with lipopolysaccharide (LPS). The effects of <i>Ifi27l2a</i> silencing were assessed through Basso Mouse Scale (BMS) scoring, inclined plane testing, hematoxylin and eosin (H&amp;E) and Nissl staining, quantitative real-time PCR (qRT-PCR), western blotting, and immunofluorescence. <i>Ifi27l2a</i> expression was markedly upregulated in microglia of mice with SCI. AAV delivery of sh-Ifi27l2a in SCI mice improved motor function and decreased neuronal death, as evidenced by increased BMS score, greater inclined plane angles, and increased Nissl bodies. sh-Ifi27l2a downregulated the expression of the M1-type marker inducible nitric oxide synthase (iNOS), and pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, while upregulating the M2 marker Arginase-1 and the anti-inflammatory cytokine IL-10. The effects of <i>Ifi27l2a</i> silencing on the M1/M2 polarization balance were confirmed in LPS-stimulated BV-2 cells. Bioinformatic prediction identified JAK2/STAT3 as a potential downstream signaling of <i>Ifi27l2a</i>. The modulatory effects of <i>Ifi27l2a</i> silencing on microglial polarization were partially mediated by JAK2/STAT3 signaling. <i>Ifi27l2a</i> expression was upregulated in the microglia of SCI mice. Silencing <i>Ifi27l2a</i> at the injury site suppressed M1 polarization while promoting M2 polarization, primarily through inhibition of the JAK2/STAT3 signaling pathway.</p>

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Silencing of Ifi27l2a Attenuates Inflammation After Spinal Cord Injury by Regulating Microglial Polarization via JAK2/STAT3 Signaling

  • 期刊论文

  • 发表日期：

    2026年1月23日

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  • Wenhao Chen,
  • Xingkun Wang,
  • Qian Xu,
  • Heng Duan,
  • Di Pan,
  • Xinyu Wang,
  • Yuwei Su,
  • Hao Li

摘要

Microglial polarization toward M1/M2 phenotypes is crucial in modulating neuroinflammation following spinal cord injury (SCI). This study aimed to investigate the role of interferon alpha-inducible protein 27-like 2A (Ifi27l2a) in regulating microglial polarization in SCI. The expression of Ifi27l2a were analyzed using single-cell RNA sequencing. C57BL/6 mice that underwent SCI were pretreated with adeno-associated virus (AAV) carrying sh-Ifi27l2a. In vitro, BV-2 cells were transfected with si-Ifi27l2a and stimulated with lipopolysaccharide (LPS). The effects of Ifi27l2a silencing were assessed through Basso Mouse Scale (BMS) scoring, inclined plane testing, hematoxylin and eosin (H&E) and Nissl staining, quantitative real-time PCR (qRT-PCR), western blotting, and immunofluorescence. Ifi27l2a expression was markedly upregulated in microglia of mice with SCI. AAV delivery of sh-Ifi27l2a in SCI mice improved motor function and decreased neuronal death, as evidenced by increased BMS score, greater inclined plane angles, and increased Nissl bodies. sh-Ifi27l2a downregulated the expression of the M1-type marker inducible nitric oxide synthase (iNOS), and pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, while upregulating the M2 marker Arginase-1 and the anti-inflammatory cytokine IL-10. The effects of Ifi27l2a silencing on the M1/M2 polarization balance were confirmed in LPS-stimulated BV-2 cells. Bioinformatic prediction identified JAK2/STAT3 as a potential downstream signaling of Ifi27l2a. The modulatory effects of Ifi27l2a silencing on microglial polarization were partially mediated by JAK2/STAT3 signaling. Ifi27l2a expression was upregulated in the microglia of SCI mice. Silencing Ifi27l2a at the injury site suppressed M1 polarization while promoting M2 polarization, primarily through inhibition of the JAK2/STAT3 signaling pathway.