The Role of Keratins and Keratinocytes in Innate Defense

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (10 June 2019) | Viewed by 18044

Special Issue Editor


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Guest Editor
Institute of Biology & SIKT, University of Leipzig, Leipzig, Germany

Special Issue Information

Dear Colleagues,

Epithelia are characterized by the expression of cytoskeletal keratin intermediate filament proteins, which support efficient barriers, strong intercellular adhesion complexes and contribute to the maintenance of tissue homeostasis by controlling inflammatory signaling. Keratin diseases such as epidermolysis bullosa simplex and pachyonychia congenita are characterized by cell and tissue fragility, inflammation, itch and the upregulation of pro-inflammatory cytokines. These events are triggered by barrier defects or by keratinocyte-intrinsic signals, which can result from keratin mutations. Conversely, microbial ligands can trigger the generation of antimicrobial peptides from keratin 6a in corneal keratinocytes to dampen immune responses. Advances in understanding how keratin interactions and mutations cause cell and tissue injury and how keratin isotypes affect inflammatory signaling in epithelial cells have delivered novel insights into disease pathomechanisms and have highlighted similarities between keratins and additional intermediate filament proteins. This knowledge may serve as a basis for concepts to restore epithelial barriers and for the development of molecular therapies.
In this Special Issue, we invite your contribution, either in the form of original research articles or reviews, providing functional and mechanistic insights, on aspects of how keratins and related intermediate filament proteins contribute to innate immune responses.

Prof. Dr. Thomas Magin
Guest Editor

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Published Papers (1 paper)

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Review

14 pages, 1155 KiB  
Review
Keratin 6, 16 and 17—Critical Barrier Alarmin Molecules in Skin Wounds and Psoriasis
by Xiaowei Zhang, Meimei Yin and Ling-juan Zhang
Cells 2019, 8(8), 807; https://doi.org/10.3390/cells8080807 - 1 Aug 2019
Cited by 206 | Viewed by 17407
Abstract
Located at the skin surface, keratinocytes (KCs) are constantly exposed to external stimuli and are the first responders to invading pathogens and injury. Upon skin injury, activated KCs secrete an array of alarmin molecules, providing a rapid and specific innate immune response against [...] Read more.
Located at the skin surface, keratinocytes (KCs) are constantly exposed to external stimuli and are the first responders to invading pathogens and injury. Upon skin injury, activated KCs secrete an array of alarmin molecules, providing a rapid and specific innate immune response against danger signals. However, dysregulation of the innate immune response of KCs may lead to uncontrolled inflammation and psoriasis pathogenesis. Keratins (KRT) are the major structural intermediate filament proteins in KCs and are expressed in a highly specific pattern at different differentiation stages of KCs. While KRT14-KRT5 is restricted to basal proliferative KCs, and KRT10-KRT1 is restricted to suprabasal differentiated KCs in normal skin epidermis, the wound proximal KCs downregulate KRT10-K1 and upregulate KRT16/KRT17-KRT6 upon skin injury. Recent studies have recognized KRT6/16/17 as key early barrier alarmins and upregulation of these keratins alters proliferation, cell adhesion, migration and inflammatory features of KCs, contributing to hyperproliferation and innate immune activation of KCs in response to an epidermal barrier breach, followed by the autoimmune activation of T cells that drives psoriasis. Here, we have reviewed how keratins are dysregulated during skin injury, their roles in wound repairs and in initiating the innate immune system and the subsequent autoimmune amplification that arises in psoriasis. Full article
(This article belongs to the Special Issue The Role of Keratins and Keratinocytes in Innate Defense)
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