A subpopulation of CD163-positive macrophages is classically activated in psoriasis.
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.
Fuentes-Duculan
Judilyn
J
Laboratory for Investigative Dermatology, Rockefeller University, New York, New York 10065, USA.
Suárez-Fariñas
Mayte
M
Zaba
Lisa C
LC
Nograles
Kristine E
KE
Pierson
Katherine C
KC
Mitsui
Hiroshi
H
Pensabene
Cara A
CA
Kzhyshkowska
Julia
J
Krueger
James G
JG
Lowes
Michelle A
MA
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
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