GSE108718
Resistin-like molecule a provides vitamin A-dependent antimicrobial protection of the skin
The skin is the human body's largest organ and is in contact with a diverse community of microorganisms  that includes both resident and pathogenic bacteria. Skin immune defenses include the production of  antimicrobial proteins that kill bacteria directly. However, we still have an incomplete understanding of  how skin antimicrobial proteins promote homeostasis with resident bacterial communities and limit  infection. Here, we show that resistin-like molecule a (RELMa) is an antibacterial protein that is produced  by keratinocytes and sebocytes in the mouse skin. RELMa expression was induced in mouse skin by  resident and pathogenic skin bacteria and was bactericidal for several bacterial species found on the skin,  including Streptococcus pyogenes. Mice lacking RELMa had altered resident skin bacterial communities  and were more susceptible to bacterial infection, indicating that RELMa controls bacterial colonization of  the skin. RELMa expression required dietary vitamin A and could be induced by therapeutic retinoids that  protected against bacterial infection in a RELMa-dependent manner. Resistin, another member of the  RELM family, was expressed in human skin, required retinoids for expression, and killed skin bacteria,  indicating a conserved function for RELM proteins in skin innate immunity. Our findings thus identify  members of the RELM family as antibacterial proteins that provide vitamin A-dependent antimicrobial  protection of the skin, and provide insight into why skin immunity requires adequate dietary vitamin A. Overall design: Skin transcriptomes from 6 germ-free mice,  3 germ-free mice colonized with Staphylococcus aureus, 3 conventional mice on a control diet and 2 conventional mice on a vitamin A deprived diet were analyzed in this study