PMID- 23664188 OWN - NLM STAT- MEDLINE DCOM- 20140121 LR - 20220129 IS - 1873-569X (Electronic) IS - 0923-1811 (Linking) VI - 71 IP - 1 DP - 2013 Jul TI - Invariant natural killer T cells are enriched at the site of cutaneous inflammation in lupus erythematosus. PG - 22-8 LID - S0923-1811(13)00127-8 [pii] LID - 10.1016/j.jdermsci.2013.04.012 [doi] AB - 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 Valpha24(+)Vbeta11(+) 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-gamma and CCR4. CONCLUSION: 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. CI - Copyright (c) 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved. FAU - Hofmann, Silke C AU - Hofmann SC AD - Centre for Rheumatology Research, University College London, UK. silke.hofmann@helios-kliniken.de FAU - Bosma, Anneleen AU - Bosma A FAU - Bruckner-Tuderman, Leena AU - Bruckner-Tuderman L FAU - Vukmanovic-Stejic, Milica AU - Vukmanovic-Stejic M FAU - Jury, Elizabeth C AU - Jury EC FAU - Isenberg, David A AU - Isenberg DA FAU - Mauri, Claudia AU - Mauri C LA - eng GR - 18106/ARC_/Arthritis Research UK/United Kingdom GR - 19314/VAC_/Versus Arthritis/United Kingdom GR - 17707/ARC_/Arthritis Research UK/United Kingdom GR - 18106/VAC_/Versus Arthritis/United Kingdom GR - 20085/ARC_/Arthritis Research UK/United Kingdom GR - 17707/VAC_/Versus Arthritis/United Kingdom GR - 19314/ARC_/Arthritis Research UK/United Kingdom GR - G0901102/MRC_/Medical Research Council/United Kingdom GR - 20085/VAC_/Versus Arthritis/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130419 PL - Netherlands TA - J Dermatol Sci JT - Journal of dermatological science JID - 9011485 RN - 0 (Biomarkers) RN - 0 (CCR4 protein, human) RN - 0 (CCR6 protein, human) RN - 0 (CD3 Complex) RN - 0 (IFNG protein, human) RN - 0 (Inflammation Mediators) RN - 0 (Receptors, Antigen, T-Cell) RN - 0 (Receptors, Antigen, T-Cell, alpha-beta) RN - 0 (Receptors, CCR4) RN - 0 (Receptors, CCR6) RN - 0 (Valpha24 protein, human) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Biomarkers/analysis MH - Biopsy MH - CD3 Complex/analysis MH - Case-Control Studies MH - Female MH - Flow Cytometry MH - Fluorescent Antibody Technique MH - Humans MH - Immunophenotyping/methods MH - Inflammation Mediators/analysis MH - Interferon-gamma/analysis MH - Lupus Erythematosus, Cutaneous/*immunology/pathology MH - Lupus Erythematosus, Discoid/immunology/pathology MH - Lupus Erythematosus, Systemic/*immunology/pathology MH - Male MH - Middle Aged MH - Natural Killer T-Cells/*immunology MH - Phenotype MH - Prospective Studies MH - Receptors, Antigen, T-Cell/analysis MH - Receptors, Antigen, T-Cell, alpha-beta/analysis MH - Receptors, CCR4/analysis MH - Receptors, CCR6/analysis MH - Skin/*immunology/pathology MH - Young Adult EDAT- 2013/05/15 06:00 MHDA- 2014/01/22 06:00 CRDT- 2013/05/14 06:00 PHST- 2012/09/15 00:00 [received] PHST- 2013/03/03 00:00 [revised] PHST- 2013/04/04 00:00 [accepted] PHST- 2013/05/14 06:00 [entrez] PHST- 2013/05/15 06:00 [pubmed] PHST- 2014/01/22 06:00 [medline] AID - S0923-1811(13)00127-8 [pii] AID - 10.1016/j.jdermsci.2013.04.012 [doi] PST - ppublish SO - J Dermatol Sci. 2013 Jul;71(1):22-8. doi: 10.1016/j.jdermsci.2013.04.012. Epub 2013 Apr 19.