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Increased Bacterial Load and Expression of Antimicrobial Peptides in Skin of Barrier-Deficient Mice with Reduced Cancer Susceptibility

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Title: Increased Bacterial Load and Expression of Antimicrobial Peptides in Skin of Barrier-Deficient Mice with Reduced Cancer Susceptibility
Authors: Natsuga, Ken Browse this author →KAKEN DB
Cipolat, Sara Browse this author
Watt, Fiona M. Browse this author
Issue Date: Jan-2016
Publisher: Elsevier
Journal Title: Journal of investigative dermatology
Volume: 136
Issue: 1
Start Page: 99
End Page: 106
Publisher DOI: 10.1038/JID.2015.383
PMID: 26422382
Abstract: Mice lacking three epidermal barrier proteins -- envoplakin, periplakin, and involucrin (EPI-/- mice) -- have a defective cornified layer, reduced epidermal γδ T cells, and increased dermal CD4+ T cells. They are also resistant to developing skin tumors. The tumor-protective mechanism involves signaling between Rae-1 expressing keratinocytes and the natural killer group 2D receptor on immune cells, which also plays a role in host defenses against infection. Given the emerging link between bacteria and cancer, we investigated whether EPI-/- mice have an altered skin microbiota. The bacterial phyla were similar in wild-type and EPI-/- skin. However, bacteria were threefold more abundant in EPI-/- skin and penetrated deeper into the epidermis. The major epithelial defense mechanism against bacteria is production of antimicrobial proteins (AMPs). EPI-/- skin exhibited enhanced expression of antimicrobial peptides. However, reducing the bacterial load by antibiotic treatment or breeding mice under specific pathogen-free conditions did not reduce AMP expression or alleviate the abnormalities in T-cell populations. We conclude that the atopic characteristics of EPI-/- skin are a consequence of the defective barrier rather than a response to the increased bacterial load. It is therefore unlikely that the increase in skin microbiota contributes directly to the observed cancer resistance.
Type: article
Appears in Collections:北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 夏賀 健

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