向纤维细胞TNF受体1减弱了17型皮肤炎症
Kellen J Cavagnero1, Fengwu Li1, Carlos Aguilera1
1Department of Dermatology, University of California, San Diego, La Jolla, CA 92093, USA.
Cell reports
|August 13, 2025
概括
瘤亡因子 (TNF) 在皮肤纤维细胞中发出信号,导致因特勒维金-17 (IL-17) 介导疾病的炎症. 向纤维细胞中TNF受体1 (TNFR1) 可能为皮肤疾病提供新的治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 皮肤病学 皮肤病学
- 细胞生物学 细胞生物学
背景情况:
- 纤维细胞越来越多地被认为是在上皮屏障上免疫细胞招募的关键调节者.
- 介导IL-17的皮肤疾病涉及复杂的炎症途径,其中纤维细胞的作用正在研究中.
研究的目的:
- 研究纤维细胞在IL-17介导的皮肤疾病中的作用.
- 为了确定参与纤维细胞驱动炎症的关键分子通路.
主要方法:
- 从人类牛皮皮肤单细胞转录组数据的分析.
- 使用TNF刺激的培养纤维细胞的功能研究.
- 用TNF抑制剂治疗的患者皮肤的转录组分析.
- 开发和使用患有纤维细胞特异性TNFR1缺陷的小鼠.
主要成果:
- 瘤亡因子 (TNF) 通过TNF受体1 (TNFR1) 的识别是牛皮皮肤中免疫作用纤维细胞中最上调的途径.
- 在培养的纤维细胞中TNF诱导的TNFR1-依赖的中性粒细胞化学激素表达.
- 在用TNF抑制剂治疗的患者中,纤维细胞衍生的中性粒细胞化学基因表达取决于TNF.
- 纤维细胞特异性TNFR1淘汰赛小鼠表现出皮肤中性粒细胞招募受损.
结论:
- 免疫作用纤维细胞中的TNF信号传递是17型皮肤炎症的关键驱动因素.
- 这一发现挑战了既定观点,即TNF主要通过皮肤炎症中的角质细胞起作用.
- 准纤维细胞TNFR1信号传递代表了IL-17驱动皮肤疾病的潜在治疗途径.
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