دورية
Epidermis-Intrinsic Transcription Factor Ovol1 Coordinately Regulates Barrier Maintenance and Neutrophil Accumulation in Psoriasis-Like Inflammation
| العنوان: | Epidermis-Intrinsic Transcription Factor Ovol1 Coordinately Regulates Barrier Maintenance and Neutrophil Accumulation in Psoriasis-Like Inflammation |
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| المؤلفون: | Dragan, Morgan, Sun, Peng, Chen, Zeyu, Ma, Xianghui, Vu, Remy, Shi, Yuling, Villalta, S. Armando, Dai, Xing |
| المصدر: | Journal of Investigative Dermatology; 20210101, Issue: Preprints |
| مستخلص: | Skin epidermis constitutes the exterior barrier that protects the body from dehydration and environmental assaults. Barrier defects underlie common inflammatory skin diseases, but the molecular mechanisms that maintain barrier integrity and regulate epidermal–immune cell cross-talk in inflamed skin are not fully understood. In this study, we show that skin epithelia-specific deletion of Ovol1, which encodes a skin disease‒linked transcriptional repressor, impairs the epidermal barrier and aggravates psoriasis-like skin inflammation in mice in part by enhancing neutrophil accumulation and abscess formation. Through molecular studies, we identify IL-33, a cytokine with known pro-inflammatory and anti-inflammatory activities, and Cxcl1,a neutrophil-attracting chemokine, as potential weak and strong direct targets of Ovol1, respectively. Furthermore, we provide functional evidence that elevated Il33expression reduces disease severity in imiquimod-treated Ovol1-deficient mice, whereas persistent accumulation and epidermal migration of neutrophils exacerbate it. Collectively, our study uncovers the importance of an epidermally expressed transcription factor that regulates both the integrity of the epidermal barrier and the behavior of neutrophils in psoriasis-like inflammation. |
| قاعدة البيانات: | Supplemental Index |
| تدمد: | 0022202X 15231747 |
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| DOI: | 10.1016/j.jid.2021.08.397 |