Knock‐down of filaggrin does not affect lipid organization and composition in stratum corneum of reconstructed human skin equivalents

Drongelen, Vincent van; Alloul-Ramdhani, Mariam; Danso, Mogbekeloluwa O.; Mieremet, Arnout; Mulder, Aat A.; Smeden, Jeroen van; Bouwstra, Joke A.; Ghalbzouri, Abdoelwaheb El

doi:10.1111/exd.12271

Cited by 44 publications

(40 citation statements)

References 46 publications

(49 reference statements)

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“…Filaggrin, for example, is only one of many molecules in epidermal differentiation complex (EDC) 142 . Knock-down of filaggrin alone was not sufficient to affect lipid composition and permeability in an ex vivo skin model 143 . Several other EDC molecules play an equally critical role in epithelial homeostasis and are frequently downregulated with filaggrin in AD, independently of filaggrin genotype or atopic status 8 .…”

Section: Identifying Key Drivers Of Defects and The Basis For Prementioning

confidence: 94%

Etiology of epithelial barrier dysfunction in patients with type 2 inflammatory diseases

Schleimer

Berdnikovs

2017

Journal of Allergy and Clinical Immunology

131

120

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Epithelial barriers of the skin, gastrointestinal tract and airway serve common critical functions such as maintaining a physical barrier against environmental insults and allergens, as well as providing a tissue interface balancing the communication between the internal and external environments. We now understand that in allergic disease, regardless of tissue location, the homeostatic balance of the epithelial barrier is skewed towards loss of differentiation, reduced junctional integrity and impaired innate defense. Importantly, epithelial dysfunction characterized by these traits appears to pre-date atopy and development of allergic disease. Despite our growing appreciation of the centrality of barrier dysfunction in the initiation of allergic disease, many important questions remain to be answered regarding the mechanisms disrupting the normal barrier function. Although our external environment (proteases, allergens, injury) is classically thought of as a principal contributor to barrier disruption associated with allergic sensitization, there is a need to better understand contributions of the internal environment (hormones, diet, circadian clock). Systemic drivers of disease, such as alterations of the endocrine system, metabolism and aberrant control of developmental signaling, are emerging as new players in driving epithelial dysfunction and allergic predisposition at various barrier sites. Identifying such central mediators of epithelial dysfunction, using both systems biology tools and causality-driven laboratory experimentation, will be essential in building new strategic interventions to prevent or reverse the process of barrier loss in allergy.

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Section: Identifying Key Drivers Of Defects and The Basis For Prementioning

confidence: 94%

Etiology of epithelial barrier dysfunction in patients with type 2 inflammatory diseases

Schleimer

Berdnikovs

2017

Journal of Allergy and Clinical Immunology

131

120

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“…However, it is not clear whether this phenomenon translates to humans. For example, filaggrin knock-down alone did not affect the permeability, lipid organization or composition of the stratum corneum in an ex vivo human skin model (32). Moreover, in AD patients with and without FLG mutations who were sensitized on healthy skin by cutaneous application of 2,4-dinitrochlorobenzene (DNCB), equal penetration of the skin and similar Th2 skewed DNCB-specific T cell responses were observed between groups (33).…”

Section: Barrier Defects and The Epidermismentioning

confidence: 99%

Skin Barrier Defects in Atopic Dermatitis

Agrawal

Woodfolk

2014

Curr Allergy Asthma Rep

152

118

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Atopic dermatitis (AD) is a chronic inflammatory skin condition with complex etiology that is dependent upon interactions between the host and the environment. Acute skin lesions exhibit the features of a Th2-driven inflammatory disorder and many patients are highly atopic. The skin barrier plays key roles in immune surveillance and homeostasis, and in preventing penetration of microbial products and allergens. Defects that compromise the structural integrity, or else the immune function of the skin barrier play a pivotal role in the pathogenesis of AD. This article provides an overview of the array of molecular building blocks that are essential to maintaining healthy skin. The basis for structural defects in the skin is discussed in relation to AD, with an emphasis on filaggrin and its genetic underpinnings. Aspects of innate immunity, including the role of anti-microbial peptides and proteases are also discussed.

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“…2 Although the impact of FLG LOF on skin barrier function is less certain. 3 While mutations of FLG are relatively common in Asian and European children with AD they were very infrequently found in those of African ancestry. 2;4 …”

Section: Introductionmentioning

confidence: 99%

“…8 Like FLG, the production of FLG2 protein has also been shown to be diminished in those with AD and in the presence of inflammatory mediators. 3;6 s1…”

Section: Introductionmentioning

confidence: 99%