Morphology of Filaggrin-Depleted Epidermis
Depletion of filaggrin results in dose-dependent impairment of epidermal permeability barrier function, which is characterized by distinctive morphological changes best detectable in ichthyosis vulgaris. In addition to increased skin surface pH, epidermal
- PDF / 1,717,700 Bytes
- 13 Pages / 504.57 x 720 pts Page_size
- 73 Downloads / 166 Views
Morphology of Filaggrin-Depleted Epidermis Robert Gruber
Contents 2.1
Sparse Inflammatory Infiltrates, Decreased Stratum Corneum Hydration, and Increased Skin Surface pH in FLG-Depleted Epidermis.........................
10
Distinctive Corneocyte Abnormalities and Altered Epidermal Homeostasis in FLG-Depleted Epidermis.........................
10
Defective Corneocyte Integrity in Filaggrin-Depleted Stratum Corneum ...
11
Impaired Epidermal Permeability Barrier Function Due to Increased Paracellular Permeability in Filaggrin-Depleted Epidermis .................
13
Abnormal Extracellular Lamellar Bilayer Architecture Due to Impaired Loading of Secretory Cargo Within Lamellar Bodies and Nonuniform Extracellular Dispersion of Secreted Contents in FLG-Depleted Stratum Corneum ........................................................
15
Defective Corneocyte Cohesion Based on Decreased Corneodesmosome Density and Length and Abnormalities in Tight Junction Protein Expression in FLG-Depleted Epidermis.........................
15
References ...............................................................
20
2.2
2.3 2.4
2.5
2.6
R. Gruber, MD Department of Dermatology and Venereology, Innsbruck Medical University, Anichstraße 35, Innsbruck 6020, Austria e-mail: [email protected]
In filaggrin-depleted epidermis, the amount of the protein filaggrin is more or less reduced, which leads to multiple morphological changes mainly in the stratum granulosum (SG) and stratum corneum (SC) and consequently to abnormalities in epidermal permeability barrier function [1]. The correlation between filaggrin deficiency and barrier abnormality can primarily be investigated in ichthyosis vulgaris (IV), the most prevalent disorder of cornification in humans, which is characterized by the postnatal onset of a generalized fine scaling phenotype, and associated with palmoplantar hyperlinearity, keratosis pilaris, and atopic dermatitis (AD) [2–6], because this skin disease is caused by loss-of-function mutations in the filaggrin gene (FLG) [7]. Mutations result in a truncated pro-filaggrin protein, which is not further processed into functional filaggrin monomers [8]. In IV, which is inherited in a semidominant way, phenotype severity appears to be subject to a dose effect, wherein heterozygous patients show a milder phenotype with reduced filaggrin, whereas homozygous or compound heterozygous FLG mutation carriers typically lack filaggrin and exhibit a more severe scaling phenotype with a greater predisposition for early development and more severe AD [7–11]. As approximately 25 % of individuals with AD also display FLG mutations [12, 13], the contribution of filaggrin deficiency to an abnormal barrier function was also assessed in AD [14]; however, a bias due to Th2-dominant inflammation, which secondarily compromises barrier function by multiple mechanisms [15], including an acquired reduction in filaggrin, cannot be excluded [16–18]. Furthermore,
J.P. Thyssen, H. Maibach (eds.), Filaggrin, DOI 10.1007/978-3-642-54379-1_2, ©
Data Loading...
