title: Invariant natural killer T cells are enriched at the site of cutaneous inflammation in lupus erythematosus.
abstract: BACKGROUND
  Systemic lupus erythematosus (SLE) is associated with a numerical and functional reduction of peripheral blood (PB) invariant natural killer T (iNKT) cells. Limited information exists on the role of iNKT cells in the pathogenesis of lupus erythematosus.
  
  
  OBJECTIVE
  To investigate the frequency and phenotype of iNKT cells in PB and dermal infiltrates from patients with SLE, subacute-cutaneous lupus erythematosus (SCLE) and discoid lupus erythematosus (DLE).
  
  
  METHODS
  PB was obtained from 23 SLE, 6 SCLE, and 11 DLE patients, and from 30 healthy controls. iNKT cell frequency and CCR4/CCR6 surface expression were assessed by flow cytometry. The frequency and phenotype of skin infiltrating Vα24(+)Vβ11(+) iNKT cells were investigated by immunofluorescence in lesional biopsies from 20 patients, unaffected skin from 3 patients, and from 6 healthy controls.
  
  
  RESULTS
  Lupus erythematosus patients displayed significantly lower percentages of circulating CD3(+)6B11(+) iNKT cells compared to healthy controls. Whereas CCR6 expression on iNKT cells was enhanced in active SLE patients regardless of cutaneous involvement compared to healthy controls, CCR4 was exclusively increased in patients with active cutaneous lesions. Furthermore, iNKT cells were significantly enriched in lesional skin of SLE and DLE patients, but not in unaffected skin of lupus patients. The majority of lesional iNKT cells expressed IFN-γ and CCR4.
  
  
  CONCLUSIONS
  The deficiency in circulating iNKT cells in cutaneous lupus erythematosus is associated with an increase of iNKT cells at the site of cutaneous inflammation. These data underscore the importance of analyzing iNKT cells not only in PB, but also in the target tissues.
authors.affiliation: Centre for Rheumatology Research, University College London, UK. silke.hofmann@helios-kliniken.de
authors.forename: Silke C
authors.initials: SC
authors.lastname: Hofmann
authors.forename: Anneleen
authors.initials: A
authors.lastname: Bosma
authors.forename: Leena
authors.initials: L
authors.lastname: Bruckner-Tuderman
authors.forename: Milica
authors.initials: M
authors.lastname: Vukmanovic-Stejic
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Jury
authors.forename: David A
authors.initials: DA
authors.lastname: Isenberg
authors.forename: Claudia
authors.initials: C
authors.lastname: Mauri
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D017252:CD3 Complex / Q000032:analysis; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D018836:Inflammation Mediators / Q000032:analysis; D007371:Interferon-gamma / Q000032:analysis; D008178:Lupus Erythematosus, Cutaneous / Q000276:immunology* / Q000473:pathology; D008179:Lupus Erythematosus, Discoid / Q000276:immunology / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000276:immunology*; D010641:Phenotype; D011446:Prospective Studies; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D054398:Receptors, CCR4 / Q000032:analysis; D054399:Receptors, CCR6 / Q000032:analysis; D012867:Skin / Q000276:immunology* / Q000473:pathology; D055815:Young Adult
chemical_list: D015415:Biomarkers; C515354:CCR4 protein, human; C106311:CCR6 protein, human; D017252:CD3 Complex; C573415:IFNG protein, human; D018836:Inflammation Mediators; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D054398:Receptors, CCR4; D054399:Receptors, CCR6; C528689:Valpha24 protein, human; D007371:Interferon-gamma