Decreased TJ Components in Atopic Dermatitis: A Possible Mechanism of Impaired Outside-In Barrier in Atopic Dermatitis

In this study, we examined changes in the TJ barrier in atopic dermatitis associated with a defective outside-in barrier. We then investigated the relationship between the TJ barrier and the outside-in barrier using a human skin equivalent with weakened TJ barrier.An analysis of DNA microarrays in atopic dermatitis showed diminished amounts of claudin-1, -4, -7, -8 and -17 mRNAs. Immunohistochemical and western blot analyses revealed diminished expression of claudin-4 (including claudin-1 shown by De Benedetto et al. (2011)), but no occludin or ZO-1 was observed. Knockdown experiments of claudin-4 in human epidermal keratinocytes weakened the TJ barrier, suggesting that the TJ barrier was weakened in atopic dermatitis.We then investigated the relationship between the outside-in barrier and TJs in human skin equivalents treated with GST-C-CPE (a polypeptide with claudin-4 inhibitory property). Human skin equivalent models possess functional TJs that completely prevent the diffusion of a paracellular tracer. However, after four days of incubation with GST-C-CPE, the TJs failed to prevent the diffusion of the paracellular tracer. In this model with weakened TJ barrier, an increase in the penetration of Lucifer Yellow through the stratum corneum down to the basal layer was observed, accompanied by an impairment of pro-filaggrin and polar lipid processing.We, therefore, suggest that an impaired TJ function promoted the entry of external substances by affecting stratum corneum formation. Further, our study suggests that a weakened TJ barrier contributes to its defective Outside-In Barrier in atopic dermatitis. JSID AbstractsJournal of Dermatological ScienceVol. 69Issue 2Preview Full-Text PDF