Document Detail


The mandatory role of IL-10-producing and OX40 ligand-expressing mature Langerhans cells in local UVB-induced immunosuppression.
MedLine Citation:
PMID:  20400709     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The mechanism underlying the local UVB-induced immunosuppression is a central issue to be clarified in photoimmunology. There have been reported a considerable number of cells and factors that participate in the sensitization phase-dependent suppression, including Langerhans cells (LCs), regulatory T cells, IL-10, and TNF-alpha. The recent important finding that LC-depleted mice rather exhibit enhanced contact hypersensitivity responses urged us to re-evaluate the role of LCs along with dermal dendritic cells (dDCs) in the mechanism of UVB-induced immunosuppression. We studied the surface expression of OX40 ligand (OX40L) and the intracellular expression of IL-10 in LCs and dDCs from UVB-irradiated (300 mJ/cm(2)) skin of BALB/c mice and those migrating to the regional lymph nodes from UVB-irradiated, hapten-painted mice. In epidermal and dermal cell suspensions prepared from the UVB-irradiated skin, LCs expressed OX40L as well as CD86 and produced IL-10 at a higher level than Langerin(-) dDCs. The UVB-induced immunosuppression was attenuated by the administration of IL-10-neutralizing or OX40L-blocking Abs. In mice whose UVB-irradiated, hapten-painted skin was dissected 1 d after hapten application, the contact hypersensitivity response was restored, because this treatment allowed dDCs but not LCs to migrate to the draining lymph nodes. Moreover, LC-depleted mice by using Langerin-diphtheria toxin receptor-knocked-in mice showed impaired UVB-induced immunosuppression. These results suggest that IL-10-producing and OX40L-expressing LCs in the UVB-exposed skin are mandatory for the induction of Ag-specific regulatory T cells.
Authors:
Ryutaro Yoshiki; Kenji Kabashima; Jun-ichi Sakabe; Kazunari Sugita; Toshinori Bito; Motonobu Nakamura; Bernard Malissen; Yoshiki Tokura
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Publication Detail:
Type:  Journal Article     Date:  2010-04-16
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  184     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-20     Completed Date:  2010-07-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5670-7     Citation Subset:  AIM; IM    
Affiliation:
Department of Dermatology, University of Occupational and Environmental Health, Fukuoka, Japan. yockey@med.uoeh-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, Surface / genetics
Cell Differentiation / immunology*,  radiation effects
Female
Gene Knock-In Techniques
Immunosuppression* / methods
Intercellular Signaling Peptides and Proteins / genetics
Interleukin-10 / biosynthesis*,  radiation effects
Langerhans Cells / immunology*,  metabolism,  radiation effects
Lectins, C-Type / genetics
Ligands
Lymphocyte Activation / immunology,  radiation effects
Mannose-Binding Lectins / genetics
Membrane Glycoproteins / biosynthesis*,  radiation effects
Mice
Mice, Inbred BALB C
Organ Culture Techniques
Skin / cytology,  immunology,  radiation effects
T-Lymphocytes, Regulatory / immunology,  metabolism,  radiation effects
Tumor Necrosis Factors / biosynthesis*,  radiation effects
Ultraviolet Rays*
Chemical
Reg. No./Substance:
0/Antigens, Surface; 0/Cd207 protein, mouse; 0/Intercellular Signaling Peptides and Proteins; 0/Lectins, C-Type; 0/Ligands; 0/Mannose-Binding Lectins; 0/Membrane Glycoproteins; 0/Tnfsf4 protein, mouse; 0/Tumor Necrosis Factors; 130068-27-8/Interleukin-10; 149176-25-0/heparin-binding EGF-like growth factor

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