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皮表皮生长因子抑制由干扰素-马诱导的促炎基因表达在皮细胞的全球转录组分析中

David C Gibbs¹, Myles R McCrary^2,3, Carlos S Moreno^4,5

¹Department of Dermatology, Emory University School of Medicine, Atlanta, GA, 30322, USA.

|February 9, 2025

概括

表皮生长因子 (EGF) 可以在全球范围内减少干扰素 (IFN-γ) 在皮肤细胞中的炎症作用. 这表明EGF在调节皮肤免疫力方面发挥作用,并可能解释EGFR抑制剂引起的炎症.

科学领域:

皮肤病学皮肤病学
免疫学免疫学免疫学
分子生物学分子生物学

背景情况:

表皮生长因子受体抑制剂 (EGFRI) 通过影响干扰素-玛 (IFN-γ) 等促炎信号通路,可以引起皮肤炎症.
表皮生长因子 (EGF) 对皮肤细胞中IFN-γ信号传递的具体影响尚不清楚.
了解这种相互作用对于管理与治疗有关的副作用至关重要.

研究的目的:

为了研究EGF对IFN-γ诱导的角质细胞转录反应的全基因组影响.
阐明EGF在调节皮肤炎症中的作用.
提供关于EGFRI的副作用的见解.

主要方法:

进行了RNA测序 (RNA-seq) 在用IFN-γ,EGF,两者,或没有治疗的人类角质细胞 (HaCaT) 细胞上.
使用DESeq2进行了差异基因表达分析,错误发现率 (FDR) 为0.01.
使用牛皮患者数据进行了基因组丰富分析和体内相关性研究.

主要成果:

补充EGF显著降低了75%的IFN-γ诱导基因的差异表达.
关键的IFN-γ诱导基因,包括CXCL10和GBP5,在EGF治疗后表达较低.
在体内研究证实,CXCL10,GBP5和相关通路在皮肤表达较低,EGF表达较高.

结论:

在全球范围内,EGF减弱了皮细胞中促炎性IFN-γ诱导的转录组.
EGF在皮肤中表现出免疫调节作用.
这些发现为EGF信号传递的非正规功能和EGFRI诱导的皮肤炎症背后的机制提供了洞察力.

关键词:

癌症癌症癌症癌症皮表皮肤生长因子皮表皮肤生长因子受体 (EGFR)免疫调节是一种免疫调节.干扰素干扰素干扰素氨酸细胞 (keratinocyte) 是一种细胞.在RNA-seqqq.皮肤皮肤皮肤皮肤文字转录学 (Transcriptomics) 是一个学科.

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