Keratin-dependent thymic stromal lymphopoietin expression suggests a link between skin blistering and atopic disease

Desmosomes and Intermediate Filaments: Their Consequences for Tissue Mechanics

“…EBS is characterized by cytoplasmic keratin aggregates, cytolysis of basal keratinocytes, and bullous lesions following mild trauma to the skin. Although it is recognized that the pathomechanisms contributing to EBS and additional keratinopathies are more complex than originally considered Roth et al 2012;Bohnekamp et al 2015;Hobbs et al 2016;Kumar et al 2016), it is evident that loss of an intact keratin cytoskeleton renders keratinocytes fragile on mild physical stress, shown by KRT5 and KRT14 KO mice (Lloyd et al 1995;Peters et al 2001). Of note, even mutations causing severe disease do not prevent formation of long keratin intermediate filaments (KIFs) in vitro (Herrmann et al 2002), suggesting that mutations and physical stress act at the level of keratin bundling, network organization, dynamics, or by affecting association with other proteins.…”

“…Cite this article as Cold Spring Harb Perspect Biol 2017;9:a029157 Deletion and/or mutation of other keratin isotypes expressed in different epidermal compartments, either in the mouse or in humans, did not cause cytolysis and skin blistering to the same extent as KRT5 and KRT14, but was typified by altered cell and tissue growth, barrier, and immune defects (Reichelt et al 2001;McGowan et al 2002;Lessard and Coulombe 2012;Roth et al 2012;Fischer et al 2014Fischer et al , 2016Fu et al 2014;Kumar et al 2016;Bouameur and Magin 2017). Transgenic expression of a bundling-competent KRT5/KRT8 chimaera partially rescued KRT5 2/2 mice, whereas expression of bundling-deficient KRT8 did not, providing strong evidence that, in addition to keratin abundancy, isotype-specific properties and keratin network organization are crucial contributors to keratin-mediated stress resilience (Alvarado and Coulombe 2014).…”

A novel mutation of keratin 5 in epidermolysis bullosa simplex with migratory circinate erythema

“…In addition, pruritus is a common problem in patients with EB which is seen up to 85% of the patients . Recently, keratins are suggested to contribute to itch in various skin disorders via inflammatory and barrier dysfunction . Although the exact mechanism of pruritus in EB is unknown, keratin mutation might play a role in EBS.…”

Regulation of Expression of Keratins and their Pathogenic Roles in Keratinopathies

“…Keratin 8 also protects colonic epithelium from inflammation, and cancer progression [22,23] Wild-type keratins suppress TSLP production. Normal human epidermal keratinocytes do not produce TSLP in culture, while keratin null keratinocytes produce copious amount of TSLP [24]. They showed that defects in keratins caused activation of MEK1/2 and ERK1/2, resulting in TSLP production independent on barrier disruption.…”