Ultraviolet radiation-induced injury, chemokines, and leukocyte recruitment: An amplification cycle triggering cutaneous lupus erythematosus.

Détails

ID Serval
serval:BIB_961320F03C0C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Ultraviolet radiation-induced injury, chemokines, and leukocyte recruitment: An amplification cycle triggering cutaneous lupus erythematosus.
Périodique
Arthritis and Rheumatism
Auteur(s)
Meller S., Winterberg F., Gilliet M., Müller A., Lauceviciute I., Rieker J., Neumann N.J., Kubitza R., Gombert M., Bünemann E., Wiesner U., Franken-Kunkel P., Kanzler H., Dieu-Nosjean M.C., Amara A., Ruzicka T., Lehmann P., Zlotnik A., Homey B.
ISSN
0004-3591 (Print)
ISSN-L
0004-3591
Statut éditorial
Publié
Date de publication
2005
Volume
52
Numéro
5
Pages
1504-1516
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
OBJECTIVE: To investigate the activation and recruitment pathways of relevant leukocyte subsets during the initiation and amplification of cutaneous lupus erythematosus (LE).
METHODS: Quantitative real-time polymerase chain reaction was used to perform a comprehensive analysis of all known chemokines and their receptors in cutaneous LE lesions, and the cellular origin of these chemokines and receptors was determined using immunohistochemistry. Furthermore, cytokine- and ultraviolet (UV) light-mediated activation pathways of relevant chemokines were investigated in vitro and in vivo.
RESULTS: In the present study, we identified the CXCR3 ligands CXCL9 (interferon-gamma [IFNgamma]-induced monokine), CXCL10 (IFNgamma-inducible protein 10), and CXCL11 (IFN-inducible T cell alpha chemoattractant) as being the most abundantly expressed chemokine family members in cutaneous LE. Expression of these ligands corresponded with the presence of a marked inflammatory infiltrate consisting of mainly CXCR3-expressing cells, including skin-homing lymphocytes and blood dendritic cell antigen 2-positive plasmacytoid dendritic cells (PDCs). Within cutaneous LE lesions, PDCs accumulated within the dermis and were activated to produce type I IFN, as detected by the expression of the IFNalpha-inducible genes IRF7 and MxA. IFNalpha, in turn, was a potent and rapid inducer of CXCR3 ligands in cellular constituents of the skin. Furthermore, we demonstrated that the inflammatory CXCR3 ligands cooperate with the homeostatic chemokine CXCL12 (stromal cell-derived factor 1) during the recruitment of pathogenically relevant leukocyte subsets. Moreover, we showed that UVB irradiation induces the release of CCL27 (cutaneous T cell-attracting chemokine) from epidermal compartments into dermal compartments and up-regulates the expression of a distinct set of chemokines in keratinocytes.
CONCLUSION: Taken together, our data suggest an amplification cycle in which UV light-induced injury induces apoptosis, necrosis, and chemokine production. These mechanisms, in turn, mediate the recruitment and activation of autoimmune T cells and IFNalpha-producing PDCs, which subsequently release more effector cytokines, thus amplifying chemokine production and leukocyte recruitment, finally leading to the development of a cutaneous LE phenotype.
Mots-clé
Cells, Cultured, Chemokine CXCL10, Chemokine CXCL11, Chemokine CXCL9, Chemokines, CXC/immunology, Humans, Intercellular Signaling Peptides and Proteins/immunology, Leukocytes/immunology, Lupus Erythematosus, Cutaneous/immunology, Lupus Erythematosus, Cutaneous/pathology, Lymphocyte Activation, Radiation Injuries/immunology, Ultraviolet Rays/adverse effects
Pubmed
Web of science
Création de la notice
19/11/2012 19:38
Dernière modification de la notice
20/08/2019 15:58
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