The mandatory role of IL-10-producing and OX40 ligand-expressing mature Langerhans cells in local UVB-induced immunosuppression.
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.
Yoshiki
Ryutaro
R
Department of Dermatology, University of Occupational and Environmental Health, Fukuoka, Japan. yockey@med.uoeh-u.ac.jp
Kabashima
Kenji
K
Sakabe
Jun-ichi
J
Sugita
Kazunari
K
Bito
Toshinori
T
Nakamura
Motonobu
M
Malissen
Bernard
B
Tokura
Yoshiki
Y
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics; D002454:Cell Differentiation / Q000276:immunology* / Q000528:radiation effects; D005260:Female; D055879:Gene Knock-In Techniques; D066257:Heparin-binding EGF-like Growth Factor; D007165:Immunosuppression Therapy / Q000379:methods; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000528:radiation effects; D007801:Langerhans Cells / Q000276:immunology* / Q000378:metabolism / Q000528:radiation effects; D037181:Lectins, C-Type / Q000235:genetics; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology / Q000528:radiation effects; D037241:Mannose-Binding Lectins / Q000235:genetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000528:radiation effects; D051379:Mice; D008807:Mice, Inbred BALB C; D053278:OX40 Ligand; D009924:Organ Culture Techniques; D012867:Skin / Q000166:cytology / Q000276:immunology / Q000528:radiation effects; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D048069:Tumor Necrosis Factors / Q000096:biosynthesis* / Q000528:radiation effects; D014466:Ultraviolet Rays
D000954:Antigens, Surface; C498497:Cd207 protein, mouse; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D008024:Ligands; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins; D053278:OX40 Ligand; C504586:Tnfsf4 protein, mouse; D048069:Tumor Necrosis Factors; D016753:Interleukin-10