Al.; 1991). Vitamin A deficiency in humans results in markedly elevated susceptibility to skin infection and inflammation (Russell and Suter, 2012), suggesting that vitamin A also promotes immune function inside the skin. This notion is supported by the truth that therapeutic vitamin A analogs are often used to treat inflammatory skin ailments such as psoriasis and acne (Saurat, 1999; ADAMTS Like 2 Proteins Recombinant Proteins Orfanos et al., 1987; Ellis and Krach, 2001). Nevertheless, little is known about how dietary vitamin A impacts skin immunity. Here, we recognize resistin-like molecule (RELM) as a skin antimicrobial protein which is important for vitamin A-dependent resistance to skin infection. We find that bacterial colonization triggers expression of RELM in mouse skin and that RELM kills bacterial species that colonize the skin. We show that RELM shapes the composition of resident skin bacterial communities and protects against pathogenic bacterial infection in the skin. Importantly, we discover that dietary vitamin A is NIMA Related Kinase 3 Proteins Recombinant Proteins required for RELM expression, and that the therapeutic vitamin A analog isotretinoin protects against skin infection in component by means of RELM. Our findings therefore illuminate a mechanism by which vitamin A promotes innate immunity and protects against skin infection.Author Manuscript Author Manuscript Author Manuscript Outcomes Author ManuscriptRELM is expressed in the skin and expression is induced by the microbiota. As a 1st step towards understanding how skin immunity is regulated by environmental elements, we sought to recognize skin antimicrobial proteins whose expression is inducible by bacteria. We made use of whole transcriptome RNA-sequencing (RNAseq) to examine transcript abundances in the skin of germ-free mice to these in the skin of germ-free mice challenged topically with Staphylococcus aureus. This Gram-positive bacterial species resides within the nasopharynx of 30 percent from the human population and is a frequent cause of skin disease (Jenkins et al., 2015; Krismer et al., 2017; Kong et al., 2012; Kobayashi et al., 2015). Colonization with S. aureus had a broad effect on gene expression in the skin (Figure S1A and S1B). Among by far the most prominent responses to S. aureus challenge was a rise inCell Host Microbe. Author manuscript; available in PMC 2020 June 12.Harris et al.Pagethe abundance of Retnla transcripts (Figure 1A and 1B). Colonization of germ-free mice with a microbiota derived from conventionally-raised mice also elevated Retnla transcript abundance, and Retnla transcript abundance was larger in mice raised within a traditional facility as compared to germ-free mice (Figure 1C). These data establish that bacteria stimulate Retnla expression within the skin.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptRetnla encodes the protein resistin-like molecule (RELM), which belongs for the protein family members that encompasses resistin along with the resistin-like molecules (RELMs) (Banerjee and Lazar, 2001) (Figure S2A and S2B). Resistin and other RELMs have already been characterized as hormones that modulate insulin production (Steppan et al., 2001; Rajala et al., 2003). On the other hand, we lately identified that RELM can be a directly bactericidal protein that kills Gramnegative bacteria in the surface from the colon and thus promotes host-bacterial mutualism in the intestine (Propheter et al., 2017). This getting led to the hypothesis that RELM might be a bactericidal protein in the skin.RELM is recognized to become created by monocytes, white adipose tissue, and lung epithelial ce.
