TABLE I.

Multiple protective functions of mammalian SC

Function	Principal compartment	Structural basis	Chemical basis	Regulatory signals (receptors)
Permeability*†	Extracellular matrix	Lamellar bilayers	Ceramides, cholesterol, nonessential fatty acids in proper ratio	IL-1α Ca++, pH, liposensors, serine proteases through PAR2, TPRV1 and TPRV4
Antimicrobial*†	Extracellular matrix	Lamellar bilayers	Antimicrobial peptides, FFAs, Sph	1,25 (OH)2D3, IL-1α
Antioxidant†	Extracellular matrix	Lamellar bilayers	Cholesterol, FFAs, secreted vitamin E, redox gradient	?
Cohesion (integrity) → desquamation*†	Extracellular matrix	CD	Intercellular DSG1/DSC1 homodimers	pH, Ca++ (TPRV)
Mechanical/rheologic†	Corneocyte	Cornified envelope, keratin filaments	γ-Glutamyl isopeptide bonds	Ca++, CholSO4, liposensors
Chemical (antigen exclusion)*†	Extracellular matrix	Extracellular lacunae	Hydrophilic products of CD	Same as for permeability barrier
Psychosensory interface†	Extracellular matrix	Lamellar bilayers	Barrier lipids	GCs, heat (TPRV3)
Hydration†	Corneocyte	Cytosol	FLG proteolytic products, glycerol	Osmotic changes (TPRV1 and TPRV4), aquaporin 3
UV light	Corneocyte	Cytosol	Trans-urocanic acid (histidase activity)
Initiation of inflammation (1° cytokine activation)*†	Corneocyte	Cytosol	Proteolytic activation of pro-IL-1α/β	pH, serine protease activation

TPRV, Transient receptor potential vanilloid; Sph, sphingomyelin; CD, corneodesmosomes; DSG1, desmoglein 1; DSC1, desmocollin 1.

^*Regulated by SC pH.

^†Abnormal in AD.