title: B-cell maturation antigen (BCMA) activation exerts specific proinflammatory effects in normal human keratinocytes and is preferentially expressed in inflammatory skin pathologies.
abstract: TNFα is known to be expressed in human skin, regulating immune-related responses. Here we report that human normal skin keratinocytes express the members of the TNF superfamily members A proliferation-inducing ligand (APRIL; TNFSF13), B cell-activating factor (BAFF; TNFSF13B), and their receptors, B cell maturation antigen (BCMA; TNFRSF17) and transmembrane activator, calcium-modulator, and cyclophilin ligand interactor (TACI; TNFRSF13B), in a distinct spatial pattern. Our data show a differential expression of these molecules within epidermal layers and skin appendages, whereas the BAFF-specific receptor BAFFR (TNFRSF13C) is absent. Importantly, APRIL and BCMA but not BAFF or TACI are up-regulated in inflammatory skin lesions of psoriasis and squamous cell carcinomas. To explore the functional significance of this system in the skin, we assayed these receptors and ligands in cultured primary keratinocytes and HaCaT cells. We show that both cell types express BAFF, APRIL, BCMA, and TACI. Furthermore, APRIL and/or BAFF trigger nuclear factor-κB activation and IL-6 and granulocyte macrophage colony-stimulating factor (GM-CSF) expression through functional BCMA receptors, an activation inhibited by anti-BCMA short hairpin RNA. However, BAFF and/or APRIL do not induce IL-8 or TNFα production. Our data advance BCMA as an inflammation-related TNFSFR member in keratinocytes, of potential importance in the management of inflammatory skin conditions.
authors.affiliation: Laboratory of Experimental Endocrinology, University of Crete, School of Medicine, P.O. Box 2208, Heraklion 71003, Greece.
authors.forename: Vassilia-Ismini
authors.initials: VI
authors.lastname: Alexaki
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Pelekanou
authors.forename: George
authors.initials: G
authors.lastname: Notas
authors.forename: Maria
authors.initials: M
authors.lastname: Venihaki
authors.forename: Marilena
authors.initials: M
authors.lastname: Kampa
authors.forename: Valérie
authors.initials: V
authors.lastname: Dessirier
authors.forename: Sanaa
authors.initials: S
authors.lastname: Sabour-Alaoui
authors.forename: Efstathios N
authors.initials: EN
authors.lastname: Stathopoulos
authors.forename: Andreas
authors.initials: A
authors.lastname: Tsapis
authors.forename: Elias
authors.initials: E
authors.lastname: Castanas
mesh_terms: D053264:B-Cell Activating Factor / Q000235:genetics / Q000378:metabolism; D053301:B-Cell Maturation Antigen / Q000378:metabolism*; D003872:Dermatitis / Q000378:metabolism* / Q000473:pathology; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D053303:Transmembrane Activator and CAML Interactor Protein / Q000235:genetics / Q000378:metabolism; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000235:genetics / Q000378:metabolism
chemical_list: D053264:B-Cell Activating Factor; D053301:B-Cell Maturation Antigen; D015850:Interleukin-6; D016328:NF-kappa B; C108467:TNFRSF13B protein, human; C114631:TNFSF13 protein, human; C505719:TNFSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D016178:Granulocyte-Macrophage Colony-Stimulating Factor