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J Invest Dermatol . 2021 Dec 20

Antimicrobial late cornified envelope (LCE) proteins: the psoriasis risk factor LCE3B/C-del affects microbiota composition

Hanna Niehues, Danique A van der Krieken, Thomas H A Ederveen, Patrick A M Jansen, Laura van Niftrik, Rob Mesman, Mihai G Netea, Jos P H Smits, Joost Schalkwijk, Ellen H van den Bogaard, Patrick L J M Zeeuwen

Late cornified envelope (LCE) proteins are predominantly expressed in the skin and other cornified epithelia. Based on sequence similarity, this eighteen-member homologous gene family has been subdivided into six groups. The LCE3 proteins have been the focus of dermatological research, as the combined deletion of LCE3B and LCE3C genes (LCE3B/C-del) is a risk factor for psoriasis. We previously reported that LCE3B/C-del increases expression of the LCE3A gene and that LCE3 proteins exert antibacterial activity. In the current study we analyzed the antimicrobial properties of other family members and the role of LCE3B/C-del in modulation of microbiota composition of the skin and oral cavity. Differences in killing efficiency and specificity between the LCE proteins and their target microbes were found, and the amino acid content, rather than the order, of the well-conserved central domain of the LCE3A protein was found responsible for its antibacterial activity. In vivo, LCE3B/C-del correlated with a higher beta-diversity in the skin and oral microbiota. From these results we conclude that all LCE proteins possess antimicrobial activity. Tissue-specific and genotype-dependent antimicrobial protein profiles impact skin and oral microbiota composition, which could direct towards LCE3B/C-del associated dysbiosis and a possible role for microbiota in the pathophysiology of psoriasis.

PMID: 34942199