What is the 'true' function of skin?

Abstract

Conventional textbook wisdom portrays the skin as an organ that literally enwraps whatever each of us stands for as a more or less functional, individual member of the mammalian species, and has it that the skin primarily establishes, controls and transmits contacts with the external world. In addition, the skin has long been recognized to protect the organism from deleterious environmental impacts (physical, chemical,microbiological), and is well-known as crucial for the maintenance of temperature, electrolyte and fluid balance. Now, ever more studies are being published that show the skin to also operate as a huge and highly active biofactory for the synthesis,processing and/or metabolism of an astounding range of e.g. structural proteins, glycans, lipids and signaling molecules. Increasingly, it becomes appreciated that the skin, furthermore, is an integral component of the immune, nervous and endocrine systems, with numerous lines of cross-talk between these systems established intracutaneously (e.g. Ann NY Acad Sci Vol 885, 1999; Endocrine Rev 21:457-487, 2000; Physiol Rev 80:980-1020, 2001; Exp Dermatol 10: 349-367, 2001). All these emerging cutaneous functions beyond the classical image of the skin as a barrier and sensory organ are immediately relevant for many of the quandaries that clinical dermatology, dermatopathology, and dermatopharmacology are still struggling with to-date, and offer the practising dermatologist attractive new targets for therapeutic intervention. Yet, many of these skin functions are not even mentioned in dermatology textbooks and await systematic therapeutic targeting. Following a suggestion by Enno Christophers, the current 'Controversies' feature brings together an unusually diverse council of biologists and clinicians, who share their thought-provoking views with the readers and allow us to peek into the future of research in cutaneous biology, not the least by reminding us of the -- often ignored -- evolutionary and embryonal origins of our favorite organ. Hopefully, this unique discussion feature will foster an understanding of the 'true' skin functions that is both more comprehensive and more profound than conventional teaching on this topic, and will stimulate more than 'skin-deep' reflections on the full range of skin functions.

Figure 1

Prototype of invertebrate integument, vertebrate integument and its appendages.

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At least 5 different cell types in human epidermis are poised to help defend the epidermis and underlying dermis from attack by biological, chemical, or solar-derived hostile agents. This figure portrays each cell type and potentially important Toll-like receptors that may be expressed by more than one cell type. Collectively, it is implied that the overall pattern of Toll-like receptor expression will embue the epidermis with the capability to recognize and respond to a vast array of infectious insults, so as to rapidly restore cutaneous homeostasis.

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Figure 1

Different degrees of epidermal wounding elicit variable response patterns. (a) Intracorneal break up may activate antimicrobials from intra-and intercellular pools. This has not been studied so far, although the events are common. (b) Epidermal wound (fissure) extending into non-keratinized cell layer. This causes secretion of antimicrobials into the defect. Proinflammatory cytokines are released by neighboring keratinocytes. (c) Deep epidermal wound extending onto the basemen membrane. In addition to the aforementioned responses, chemokines released into the dermis will now attract neutrophils with the ability to phagocytose invading pathogens.

Figure 1

Fluorescence spectra of blood plasma samples after topical application of fluorescein-isothiocyanate (FITC) (upper curve) or solvent only (lower curve). The excitation wavelength was 488nm (band pass 2nm), the integration time was 1s. Data were taken at the emission maximum of FITC at about 517nm.

Figure 2

Fluorescein-isothiocyanate emission was recorded in blood plasma from 1min up to 72h. Error bars are median ± SD.

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Samples of mouse plasma were subjected to Sephadex G-25 column chromatography. Fluorescein-isothiocyanate (FITC) molecules bound to plasma proteins were separated from free FITC molecules. Curves illustrate that free hapten combines increasingly with plasma proteins.