title: The expression and regulation of chemerin in the epidermis.
abstract: Chemerin is a protein ligand for the G protein-coupled receptor CMKLR1 and also binds to two atypical heptahelical receptors, CCRL2 and GPR1. Chemerin is a leukocyte attractant, adipokine, and antimicrobial protein. Although chemerin was initially identified as a highly expressed gene in healthy skin keratinocytes that was downregulated during psoriasis, the regulation of chemerin and its receptors in the skin by specific cytokines and microbial factors remains unexplored. Here we show that chemerin, CMKLR1, CCRL2 and GPR1 are expressed in human and mouse epidermis, suggesting that this tissue may be both a source and target for chemerin mediated effects. In human skin cultures, chemerin is significantly downregulated by IL-17 and IL-22, key cytokines implicated in psoriasis, whereas it is upregulated by acute phase cytokines oncostatin M and IL-1β. Moreover, we show that human keratinocytes in vitro and mouse skin in vivo respond to specific microbial signals to regulate expression levels of chemerin and its receptors. Furthermore, in a cutaneous infection model, chemerin is required for maximal bactericidal effects in vivo. Together, our findings reveal previously uncharacterized regulators of chemerin expression in skin and identify a physiologic role for chemerin in skin barrier defense against microbial pathogens.
authors: Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
authors: Magdalena
authors: M
authors: Banas
authors: Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
authors: Aneta
authors: A
authors: Zegar
authors: Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
authors: Mateusz
authors: M
authors: Kwitniewski
authors: Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
authors: Katarzyna
authors: K
authors: Zabieglo
authors: Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
authors: Joanna
authors: J
authors: Marczynska
authors: Department of Dermatology, Zeromski Hospital, Kraków, Poland.
authors: Monika
authors: M
authors: Kapinska-Mrowiecka
authors: Stanford University School of Medicine, Department of Pathology, Stanford, California, United States of America; Palo Alto Veterans Institute for Research, VA Palo Alto Health Care System, Palo Alto, California, United States of America.
authors: Melissa
authors: M
authors: LaJevic
authors: Palo Alto Veterans Institute for Research, VA Palo Alto Health Care System, Palo Alto, California, United States of America.
authors: Brian A
authors: BA
authors: Zabel
authors: Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
authors: Joanna
authors: J
authors: Cichy
mesh_terms: D000818:Animals; D018925:Chemokines; D002630:Chemotactic Factors / Q000096:biosynthesis* / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004817:Epidermis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D054388:Receptors, CCR; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis / Q000235:genetics; D012871:Skin Diseases / Q000235:genetics / Q000378:metabolism* / Q000401:mortality
chemical_list: C111851:Ccrl2 protein, mouse; D018925:Chemokines; D002630:Chemotactic Factors; D016207:Cytokines; C000591279:GPR1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D054388:Receptors, CCR; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; C523686:chemerin protein, mouse