期刊
JOURNAL OF CELL SCIENCE
卷 125, 期 22, 页码 5269-5279出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.116574
关键词
Keratin cytoskeleton; Epidermal barrier; Innate immunity; Interleukin-18; Atopic eczema
类别
资金
- Thyssen Foundation [Thyssen 10.02.1.103]
- BONFOR
- Deutsche Forschungsgemeinschaft [DFG 1316/9]
- Translational Centre for Regenerative Medicine Leipzig [PtJ-Bio] [0315883]
Keratin 1 (KRT1) and its heterodimer partner keratin 10 (KRT10) are major constituents of the intermediate filament cytoskeleton in suprabasal epidermis. KRT1 mutations cause epidermolytic ichthyosis in humans, characterized by loss of barrier integrity and recurrent erythema. In search of the largely unknown pathomechanisms and the role of keratins in barrier formation and inflammation control, we show here that Krt1 is crucial for maintenance of skin integrity and participates in an inflammatory network in murine keratinocytes. Absence of Krt1 caused a prenatal increase in interleukin-18 (IL-18) and the S100A8 and S100A9 proteins, accompanied by a barrier defect and perinatal lethality. Depletion of IL-18 partially rescued Krt1(-/-) mice. IL-18 release was keratinocyte-autonomous, KRT1 and caspase-1 dependent, supporting an upstream role of KRT1 in the pathology. Finally, transcriptome profiling revealed a Krt1-mediated gene expression signature similar to atopic eczema and psoriasis, but different from Krt5 deficiency and epidermolysis bullosa simplex. Our data suggest a functional link between KRT1 and human inflammatory skin diseases.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据