title: A subpopulation of CD163-positive macrophages is classically activated in psoriasis.
abstract: Macrophages are important cells of the innate immune system, and their study is essential to gain greater understanding of the inflammatory nature of psoriasis. We used immunohistochemistry and double-label immunofluorescence to characterize CD163(+) macrophages in psoriasis. Dermal macrophages were increased in psoriasis compared with normal skin and were identified by CD163, RFD7, CD68, lysosomal-associated membrane protein 2 (LAMP2), stabilin-1, and macrophage receptor with collagenous structure (MARCO). CD163(+) macrophages expressed C-lectins CD206/macrophage mannose receptor and CD209/DC-SIGN, as well as costimulatory molecules CD86 and CD40. They did not express mature dendritic cell (DC) markers CD208/DC-lysosomal-associated membrane glycoprotein, CD205/DEC205, or CD83. Microarray analysis of in vitro-derived macrophages treated with IFN-γ showed that many of the genes upregulated in macrophages were found in psoriasis, including STAT1, CXCL9, Mx1, and HLA-DR. CD163(+) macrophages produced inflammatory molecules IL-23p19 and IL-12/23p40 as well as tumor necrosis factor (TNF) and inducible nitric oxide synthase (iNOS). These data show that CD163 is a superior marker of macrophages, and identifies a subpopulation of "classically activated" macrophages in psoriasis. We conclude that macrophages are likely to contribute to the pathogenic inflammation in psoriasis, a prototypical T helper 1 (Th1) and Th17 disease, by releasing key inflammatory products.
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, New York 10065, USA.
authors.forename: Judilyn
authors.initials: J
authors.lastname: Fuentes-Duculan
authors.forename: Mayte
authors.initials: M
authors.lastname: Suárez-Fariñas
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Zaba
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Nograles
authors.forename: Katherine C
authors.initials: KC
authors.lastname: Pierson
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mitsui
authors.forename: Cara A
authors.initials: CA
authors.lastname: Pensabene
authors.forename: Julia
authors.initials: J
authors.lastname: Kzhyshkowska
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Lowes
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism*; D001706:Biopsy; D002478:Cells, Cultured; D054370:Chemokine CXCL9 / Q000235:genetics; D003713:Dendritic Cells / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D019204:GTP-Binding Proteins / Q000235:genetics; D015870:Gene Expression / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D037181:Lectins, C-Type / Q000378:metabolism; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D064547:Myxovirus Resistance Proteins; D011565:Psoriasis / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000235:genetics; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; C080810:CXCL9 protein, human; D054370:Chemokine CXCL9; D006684:HLA-DR Antigens; D037181:Lectins, C-Type; D064547:Myxovirus Resistance Proteins; D011956:Receptors, Cell Surface; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D007371:Interferon-gamma; D019204:GTP-Binding Proteins