Langerhans cells are required for UVR-induced immunosuppression.
Painting of haptens onto UVR-exposed skin does not result in sensitization but induces regulatory T cells (Treg). This was explained by UVR-mediated depletion of Langerhans cells (LCs). Furthermore, migration of UVR-damaged but still viable LCs into lymph nodes appears to be essential to induce Treg. Accordingly, the steroid mometasone, which kills LCs, inhibited sensitization but did not induce Treg. In Langerin-diphtheria toxin receptor knock-in (DTR) mice, LCs can be depleted by injection of diphtheria toxin (DT). LC-depleted mice could be sensitized though less pronounced than wild-type mice, but sensitization was not suppressed by UVR. Similarly, Treg did not develop. Langerin is not only expressed in LCs but also in some dermal dendritic cells (dDCs). Langerin-positive dDCs repopulate within 10 days after depletion, whereas LCs are still absent. Langerin-DTR mice treated with DT 10 days before UVR and sensitization were still resistant to UVR-induced inhibition of contact hypersensitivity (CHS). Similarly, Treg did not arise. As in this setting only LCs but not Langerin-positive dDCs are absent, LCs appear to be essential for both the suppression of CHS and the induction of Treg by UVR. This supports the concept that LCs are more important for the downregulation than the induction of immune responses in the skin.
Schwarz
Agatha
A
Department of Dermatology, University Kiel, Kiel, Germany.
Noordegraaf
Madelon
M
Maeda
Akira
A
Torii
Kan
K
Clausen
Björn E
BE
Schwarz
Thomas
T
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000528:radiation effects; D003877:Dermatitis, Contact / Q000188:drug therapy / Q000276:immunology*; D020405:Dermis / Q000166:cytology / Q000276:immunology / Q000528:radiation effects; D005260:Female; D055879:Gene Knock-In Techniques; D066257:Heparin-binding EGF-like Growth Factor; D007108:Immune Tolerance / Q000276:immunology* / Q000528:radiation effects*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology* / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D000068656:Mometasone Furoate; D011244:Pregnadienediols / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000528:radiation effects; D014466:Ultraviolet Rays
D000893:Anti-Inflammatory Agents; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D011244:Pregnadienediols; D000068656:Mometasone Furoate