title: A subset of CD163+ macrophages displays mixed polarizations in discoid lupus skin.
abstract: BACKGROUND
  Lesional skin of patients with discoid lupus erythematosus (DLE) contains macrophages, whose polarization has yet to be investigated. To test our hypothesis that M1 macrophages would be increased in DLE skin, we examined transcriptome alterations in immune cell gene expression and macrophage features in DLE and normal skin by using gene expression and histochemical approaches.
  
  
  METHODS
  Gene expression of RNA from DLE lesional and normal control skin was compared by microarrays and quantitative real-time polymerase chain reaction (RT-PCR). Both skin groups were analyzed for CD163 expression by immunohistochemistry. Double immunofluorescence studies were performed to characterize protein expression of CD163+ macrophages.
  
  
  RESULTS
  DLE skin had twice as many upregulated genes than downregulated genes compared with normal skin. Gene set enrichment analysis comparing differentially expressed genes in DLE and normal skin with previously published gene sets associated with M1 and M2 macrophages showed strong overlap between upregulated genes in DLE skin and M1 macrophages. Quantitative RT-PCR showed that several M1 macrophage-associated genes--e.g., chemokine (C-X-C motif) ligand 10 (CXCL10), chemokine (C-C motif) ligand 5 (CCL5), and signal transducer and activator of transcription 1 (STAT1)-had amplified mRNA levels in DLE skin. CD163+ macrophages were increased near the epidermal-dermal junction and perivascular areas in DLE skin compared with normal skin. However, double immunofluorescence studies of CD163+ macrophages revealed minor co-expression of M1 (CXCL10, tumor necrosis factor-alpha, and CD127) and M2 (CD209 and transforming growth factor-beta) macrophage-related proteins in DLE skin.
  
  
  CONCLUSIONS
  Whereas a subset of CD163+ macrophages displays mixed polarizations in DLE skin, other immune cells such as T cells can contribute to the expression of these macrophage-related genes.
authors.affiliation: Department of Dermatology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390-9069, USA. ben.chong@utsouthwestern.edu.
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Chong
authors.affiliation: Department of Dermatology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390-9069, USA. lin-chiang.tseng@utsouthwestern.edu.
authors.forename: Lin-Chiang
authors.initials: LC
authors.lastname: Tseng
authors.affiliation: Department of Dermatology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390-9069, USA. gregory.hosler@propath.com.|ProPath, 1355 River Bend Drive, Dallas, 75247, TX, USA. gregory.hosler@propath.com.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Hosler
authors.affiliation: Department of Dermatology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390-9069, USA. noelle.teske@utsouthwestern.edu.
authors.forename: Noelle M
authors.initials: NM
authors.lastname: Teske
authors.affiliation: Department of Clinical Sciences, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, 75390, TX, USA. song.zhang@utsouthwestern.edu.
authors.forename: Song
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine, Rheumatic Diseases Division, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, 75390-8884, TX, USA. david.karp@utsouthwestern.edu.
authors.forename: David R
authors.initials: DR
authors.lastname: Karp
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, Penn State Milton S. Hershey Medical Center, Mail Code H038, Hershey, 17033-0850, PA, USA. nolsen@hmc.psu.edu.
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Olsen
authors.affiliation: Department of Biomedical Engineering, University of Houston, 500 University Drive, P.O. Box 850 3065 Cullen Street, Houston, 77204, TX, USA. cmohan@central.uh.edu.
authors.forename: Chandra
authors.initials: C
authors.lastname: Mohan
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics*; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008179:Lupus Erythematosus, Discoid / Q000235:genetics* / Q000473:pathology*; D008264:Macrophages / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000235:genetics*; D012867:Skin / Q000473:pathology*; D055815:Young Adult; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D011956:Receptors, Cell Surface