Functional redundancy of Langerhans cells and Langerin+ dermal dendritic cells in contact hypersensitivity

J Invest Dermatol. 2010 Dec;130(12):2752-9. doi: 10.1038/jid.2010.223. Epub 2010 Aug 12.

Abstract

The relative roles of Langerhans cells (LC), dermal dendritic cells (DC), and, in particular, the recently discovered Langerin(+) dermal DC subset in the induction and control of contact hypersensitivity (CHS) responses remain controversial. Using an inducible mouse model, in which LC and other Langerin(+) DC can be depleted by injection of diphtheria toxin, we previously reported impaired transport of topically applied antigen to draining lymph nodes and reduced CHS in the absence of all Langerin(+) skin DC. In this study, we demonstrate that mice with a selective depletion of LC exhibit attenuated CHS only upon sensitization with a low hapten dose but not with a high hapten dose. In contrast, when painting a higher concentration of hapten onto the skin, which leads to increased antigen dissemination into the dermis, CHS is still diminished in mice lacking all Langerin(+) skin DC. Taken together, these data suggest that the magnitude of a CHS reaction depends on the number of skin DC, which have access to the hapten, rather than on the presence or absence of a particular skin DC population. LC and (Langerin(+)) dermal DC thus seem to have a redundant function in regulating CHS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Surface / genetics*
  • Antigens, Surface / metabolism
  • Dermatitis, Contact / immunology*
  • Dermatitis, Contact / pathology*
  • Dermis / immunology
  • Dermis / pathology
  • Diphtheria Toxin / toxicity
  • Disease Models, Animal
  • Epidermis / immunology
  • Epidermis / pathology
  • Gene Knock-In Techniques
  • Haptens / immunology
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Langerhans Cells / immunology*
  • Langerhans Cells / pathology*
  • Lectins, C-Type / genetics*
  • Lectins, C-Type / metabolism
  • Mannose-Binding Lectins / genetics*
  • Mannose-Binding Lectins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Organ Culture Techniques
  • Poisons / toxicity

Substances

  • Antigens, Surface
  • Cd207 protein, mouse
  • Diphtheria Toxin
  • Haptens
  • Hbegf protein, mouse
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • Lectins, C-Type
  • Mannose-Binding Lectins
  • Poisons