Table 1.

Multiple protective functions of the outer epidermis

Function	Principal compartment	Structural basis	Biochemical basis	Regulatory signals (receptors)
Permeability*†	Extracellular matrix of SC	Lamellar bilayers	Ceramides, cholesterol, nonessential fatty acids in proper ratio	IL-1α, Ca++, pH, liposensors, serine proteases via PAR2, TPRV1 and 4
Antimicrobial*†	Extracellular matrix of SC	Lamellar bilayers	Antimicrobial peptides, FFA, sphingsine	1,25 (OH)2D3; IL-1α
Antioxidant†	Extracellular matrix of SC	Lamellar bilayers	Cholesterol, FFA, secreted vitamin E, redox gradient	?
Cohesion (integrity) → desquamation*†	Extracellular matrix of SC	Corneodesmosomes	Intercellular DSG1/DSC1 homodimers	pH, Ca++, (TPRV)
Mechanical or rheological†	Corneocyte	Cornified envelope; keratin filaments	γ-glutamyl isopeptide bonds	Ca++, CholSO4, liposensors
Chemical (antigen exclusion)*†	Extracellular matrix of SC	Extracellular lacunae	Hydrophilic products of corneodesmosomes	Same as for permeability barrier
Psychosensory interface†	Extracellular matrix of SC	Lamellar bilayers	Barrier lipids	Glucocorticoids, heat, (TPRV3)
Neurosensory	Stratum granulosum	Neuroreceptors + transmitters	Ion channels, neurotransmitters	Divalent cations; K+; others?
Hydration†	Corneocyte	Cytosolic pool of precursors	Filaggrin proteolytic products; glycerol	Osmotic changes, (TPRV1 and 4), aquaporin 3
Ultraviolet light	Corneocyte	Cytosol	Trans-urocanic acid (histidase activity)
Initiation of inflammation (first-degree cytokine activity)*†	Corneocyte	Cytosol	Proteolytic activation of pro-IL-1α/β	pH, serine protease activation

^*Regulated by SC pH.

^†Abnormal in atopic dermatitis.

FFA—free fatty acids; IL—interleukin; PAR2—plasminogen activator type 2 receptor; SC—stratum corneum.