Skin wounds breach the physical barrier that protects the body from harmful microbes in the environment. To counter this breach, wounding triggers an immune response that includes the production of antimicrobial peptides and the upregulation of receptors that recognize microbial components. However, the factors that trigger this immune response have not been well defined.
In a study appearing online on February 8 in advance of publication in the March print issue of the Journal of Clinical Investigation, Richard Gallo and colleagues from the University of California at San Diego now show that wounding to the skin of humans triggers the production (by skin cells known as keratinocytes) of the active form of vitamin D3, and that this induces increased expression of the antimicrobial peptide cathelicidin and the microbial recognition receptors TLR2 and CD14. Further analysis showed that wounding induced keratinocyte expression of the enzyme responsible for converting inactive vitamin D3 to active vitamin D3 (CYP27B1) and that this could be recapitulated in vitro by culturing keratinocytes in the presence of the soluble factor TGF-beta-1. The authors therefore suggest that soluble factors present in wounds, such as TGF-beta-1, induce the expression of CYP27B1, which enables keratinocytes to produce active vitamin D3 that, in turn, induces the upregulation of some components of the immune response and protects us from harmful microbes.
TITLE: Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D–dependent mechanism
AUTHOR CONTACT:
Richard L. Gallo
University of California at San Diego, San Diego, California, USA.
Phone: (858) 552-8585 ext. 6149; Fax: (858) 552-7436; E-mail: ragllo@ucsd.edu.
View the PDF of this article at: https://www.the-jci.org/article.php?id=30142
Journal
Journal of Clinical Investigation