Keratinocyte Proline-Rich Protein Deficiency in Atopic Dermatitis Leads to Barrier Disruption

Abstract Atopic dermatitis (AD) is a common inflammatory skin disease caused by interaction of genetic and environmental factors. By allelic copy number analysis at missense single-nucleotide polymorphisms on 26 genes with copy number variation, we identified significant association between atopic dermatitis and human keratinocyte proline-rich protein ( hKPRP ). hKPRP expression, which was localized to the upper granular layer of epidermis, was significantly decreased in AD compared to normal skin. KPRP was histologically co-localized with loricrin, and was mainly detected in cytoskeleton fractions of human keratinocytes. To further investigate the role of KPRP in skin, Kprp -knockout mice were generated. Heterozygous knockout ( Kprp +/- ) mice exhibited reduced KPRP expression to a similar level of human AD lesional skin. Kprp +/- mice showed abnormal desmosome structure and detachment of lower layers of stratum corneum. Percutaneous inflammation by topical application of croton oil or oxazolone was enhanced and epicutaneous immunization with OVA induced a high level of IgE in Kprp +/- mice. Our study, started from allelic copy number analysis in human AD, identified importance of KPRP, whose decrease leads to barrier dysfunction.