炎症
转录因子
细胞生物学
p38丝裂原活化蛋白激酶
生物
磷酸化
免疫学
过敏性炎症
化学
蛋白激酶A
基因
生物化学
作者
Yanek Jiménez-Andrade,Kathryn R. Hill,Toshimi Yoshida,Mariko Kashiwagi,Min‐Kyung Choo,Yinming Liang,Katia Georgopoulos,Jin Mo Park
出处
期刊:Journal of Immunology
[American Association of Immunologists]
日期:2022-06-15
卷期号:208 (12): 2613-2621
被引量:2
标识
DOI:10.4049/jimmunol.2101160
摘要
Abstract Keratinocytes, the epithelial cells of the skin, reprogram their gene expression and produce immune effector molecules when exposed to environmental and endogenous triggers of inflammation. It remains unclear how keratinocytes process physiological signals generated during skin irritation and switch from a homeostatic to an inflammatory state. In this article, we show that the stress-activated protein kinase p38α is crucial for keratinocytes to prompt changes in their transcriptome upon cytokine stimulation and drive inflammation in allergen-exposed skin. p38α serves this function by phosphorylating p63, a transcription factor essential for the lineage identity and stemness of the skin epithelium. Phosphorylation by p38α alters the activity of p63 and redeploys this developmental transcription factor to a gene expression program linked to inflammation. Genetic ablation and pharmacological inhibition of p38α or the p38α–p63 target gene product MMP13 attenuate atopic dermatitis–like disease in mice. Our study reveals an epithelial molecular pathway promoting skin inflammation and actionable through treatment with topical small-molecule therapeutics.
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