Editors' ChoiceHost-Microbe Interactions

How vitamin A protects the skin

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Science Signaling  16 Jul 2019:
Vol. 12, Issue 590, eaay6954
DOI: 10.1126/scisignal.aay6954

Retinoids protect the skin from infection by inducing the production of an endogenous antimicrobial protein.

The vitamin A derivative retinoic acid protects against infection because it stimulates the expression of immunity-related genes that contain retinoic acid response elements (RAREs). Vitamin A deficiency is associated with an increased susceptibility to skin infections, and retinoids are effective for treating some inflammatory skin conditions. Harris et al. found that keratinocytes and sebocytes (sebaceous gland cells) of mice produced resistin-like molecule αα (RELMα) when germ-free animals were challenged with the opportunistic pathogen Staphylococcus aureus. In vitro, RELMα and its human homolog resistin (RETN) exhibited bactericidal activity against both Gram-negative and Gram-positive species, and they permeabilized liposomes, suggesting that they may act as pore-forming, antimicrobial peptides (see commentary by Schröder). Experiments with RELMα-deficient mice indicated that RELMα played a role in shaping the composition of the skin microbiome. In a human sebaceous gland cell line, the RETN promoter, which contains putative RAREs, immunoprecipitated with retinoic acid receptors (RARs), and its activity was stimulated by retinol in the presence of the proinflammatory cytokine interleukin-1β unless RARs were pharmacologically inhibited. In mice fed a vitamin A–deficient diet, RELMα and the transcript encoding it (Retlna) were less abundant in the skin, and the animals were more susceptible to skin infection compared with controls. Oral administration of the synthetic retinoid isotretinoin stimulated Retlna expression in mice fed normal chow and rescued Retlna expression and susceptibility to infection in vitamin A–deficient mice. Although further work will be required to determine how bacteria induce Retlna expression, these findings identify an important role for vitamin A derivatives in shaping the microbial community of the skin and protecting against colonization by pathogenic bacteria.

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