LECs通过IL-17RC/CMTM4/NF-κB轴在炎症或感染部位调节中性粒细胞清除
Qiaoqi Ni1, Gen Li2, Yue Chen3
1Department of Basic Science of Stomatology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China.
Mucosal immunology
|May 16, 2024
概括
淋巴内皮细胞 (LECs) 在炎症期间吸引中性粒细胞到淋巴结. CMTM4蛋白调解了这一过程,为治疗炎症性疾病提供了潜在的点.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 血管生物学 血管生物学
背景情况:
- 淋巴系统对于液体平衡和免疫反应至关重要.
- 淋巴内皮细胞 (LEC) 在中性粒细胞迁移中的作用尚未完全理解.
- 中性粒细胞是关键的免疫细胞,参与炎症和感染.
研究的目的:
- 研究LEC在炎症和感染期间中性粒细胞迁移中的作用.
- 阐明LECs调节中性粒细胞吸引力的分子机制.
- 探索针对免疫相关疾病的LEC的治疗潜力.
主要方法:
- 皮肤炎症,皮肤感染和牙周炎的小鼠模型.
- 用细胞因子 (IL-17A,TNF-α) 进行LEC体外刺激.
- 对化基因表达和信号通路 (NF-κB) 的分析.
- 在LEC中对CMTM4表达的基因操纵.
- 在小鼠中,腺相关病毒介导的基因传递.
主要成果:
- 中性粒细胞通过淋巴血管在炎症/感染组织中迁移到排水淋巴结.
- IL-17A和TNF-α在炎症组织中的中性粒细胞吸引化学基因上调.
- IL-17A加上TNF-α协同诱导LECs的化学激素分泌.
- CMTM4与IL-17RC结合,并通过NF-κB信号传递调解IL-17A/TNF-α诱导的化学激素分泌.
- 特定于LEC的CMTM4过度表达增强了中性粒细胞的排泄,并减少了免疫病理.
结论:
- LECs在吸引和清除中性粒细胞从炎症或感染组织中发挥着重要作用.
- 这种CMTM4-IL-17RC相互作用对于LEC介导的中性粒细胞吸引是至关重要的.
- 在LEC中准CMTM4可能为炎症条件提供一种新的治疗策略.
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