title: The dermal microenvironment induces the expression of the alternative activation marker CD301/mMGL in mononuclear phagocytes, independent of IL-4/IL-13 signaling.
abstract: Recently, we have shown that mononuclear phagocytes comprise the majority of interstitial cells in the mouse dermis, as indicated by their phenotypic and functional characteristics. In particular, these cells express the mouse macrophage galactose-/N-acetylgalactosamine-specific-lectin (mMGL)/CD301, identified by the monoclonal antibody ER-MP23, as well as other macrophage markers. As expression of mMGL is induced by IL-4 or IL-13 and is therefore a marker of alternatively activated macrophages, we asked whether dermal mononuclear phagocytes are genuinely alternatively activated. We observed that these cells expressed, next to mMGL, two other alternative activation markers, namely, the mannose receptor/CD206 and Dectin-1. Yet, as this expression profile was similar in IL-4 receptor alpha knockout mice, neither IL-4 nor IL-13 signaling appeared to be required for this phenotype. We also found that Langerhans cells (LC), which showed only a low level of mMGL in the epidermis, up-regulated mMGL expression upon migration through the dermis, allowing these cells to internalize limited amounts of mMGL ligands. LC isolated from epidermal preparations did not show this up-regulation when cultured in standard medium, but whole skin-conditioned medium did stimulate mMGL expression by LC. The vast majority of mMGL molecules was present in the cytoplasm, however. LC, which arrived in skin-draining lymph nodes, quickly down-regulated mMGL expression, and dermally derived cells retained significant mMGL levels. Taken together, these data suggest that the dermal microenvironment induces mononuclear phagocyte subpopulations to express mMGL and possibly other markers of alternatively activated macrophages, independent of IL-4/IL-13 signaling.
authors.affiliation: Department of Immunology, Erasmus MC, NL-3015 GE Rotterdam, The Netherlands.
authors.forename: Marcel
authors.initials: M
authors.lastname: Dupasquier
authors.forename: Patrizia
authors.initials: P
authors.lastname: Stoitzner
authors.forename: Hui
authors.initials: H
authors.lastname: Wan
authors.forename: Denise
authors.initials: D
authors.lastname: Cerqueira
authors.forename: Adri
authors.initials: A
authors.lastname: van Oudenaren
authors.forename: Jane S A
authors.initials: JS
authors.lastname: Voerman
authors.forename: Kaori
authors.initials: K
authors.lastname: Denda-Nagai
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Irimura
authors.forename: Geert
authors.initials: G
authors.lastname: Raes
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Romani
authors.forename: Pieter J M
authors.initials: PJ
authors.lastname: Leenen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001212:Asialoglycoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D020405:Dermis / Q000166:cytology / Q000276:immunology*; D005260:Female; D018793:Interleukin-13 / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology*; D007801:Langerhans Cells / Q000276:immunology; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010586:Phagocytes / Q000276:immunology*; D011485:Protein Binding; D015398:Signal Transduction / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D001212:Asialoglycoproteins; C064720:Clec10a protein, mouse; D018793:Interleukin-13; D037181:Lectins, C-Type; C464940:MGL2 protein, mouse; D008565:Membrane Proteins; D015847:Interleukin-4