Chapter

Apoptotic and Non-apoptotic Cell Death

Volume 403 of the series Current Topics in Microbiology and Immunology pp 77-93

Date:

Epithelial Cell Death and Inflammation in Skin

  • Snehlata KumariAffiliated withInstitute for Genetics, University of CologneCologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of CologneCenter for Molecular Medicine (CMMC), University of Cologne
  • , Manolis PasparakisAffiliated withInstitute for Genetics, University of CologneCologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of CologneCenter for Molecular Medicine (CMMC), University of Cologne Email author 

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Abstract

The presence of dying cells in inflamed tissues has been recognized since many years, but until recently cell death was considered primarily a consequence of inflammation. Recent data in mouse models suggest that cell death could provide a potent trigger of inflammation. The identification of necroptosis as a new type of regulated necrotic cell death that is induced by death receptors, toll like receptors and type I interferon receptor indicated that necroptosis could contribute to the proinflammatory properties of these receptors. This is particularly relevant to the skin, a tissue that provides a life-sustaining structural and immunological barrier with the environment and is constantly exposed to mechanical, chemical, and microbial insults. Studies in mouse models showed that sensitization of keratinocytes to apoptosis or necroptosis triggered by TNF and other stimuli causes severe chronic inflammatory skin lesions. In addition, keratinocyte death is a prominent histopathological feature of many inflammatory skin diseases, suggesting that death of epithelial cells could contribute to the pathogenesis of skin inflammation . Here we review recent studies in genetic mouse models providing evidence that keratinocyte death is a potent trigger of skin inflammation and discuss their potential relevance for human inflammatory skin diseases.