The role of toll-like receptor 3 in chronic contact hypersensitivity induced by repeated elicitation

J Dermatol Sci. 2017 Nov;88(2):184-191. doi: 10.1016/j.jdermsci.2017.07.017. Epub 2017 Aug 4.


Background: Accumulating evidence suggests that Toll-like receptor (TLR)-3 signaling is involved in non-infectious immune and inflammatory reactions as well as in viral infections. The skin of patients with atopic dermatitis (AD) is often infected with virus and bacteria, leading to the aggravation of atopic symptoms. These findings suggest TLR3 signaling may be involved in the pathogenesis of AD, but the exact role of TLR3 in AD remains to be defined.

Objective: The purpose of this study was to investigate the role of TLR3 in chronic contact hypersensitivity reactions induced by repeated elicitation, resembling the features of AD.

Methods: Wild-type (WT) and Toll-like receptor 3 knockout (Tlr3 KO) mice were sensitized, and chronic contact hypersensitivity reactions were elicited in their ear skin via repeated application of a hapten, 2,4,6-trinitro-1-chlorobenzene (TNCB) or oxazolone.

Results: The Tlr3 KO mice exhibited less ear swelling, less leukocyte infiltration into the skin, and lower serum total IgE levels than WT mice after hapten challenge. The Tlr3 KO mice also displayed lower expression levels of inflammatory cytokines (interleukin (IL)-33, IL-4, IL-10, and interferon-ɤ in their TNCB-treated ear skin than WT mice.

Conclusion: These results showed that TLR3 deficiency suppressed the development of chronic contact hypersensitivity reactions, suggesting that TLR3 signaling may participate in the pathogenesis of AD.

Keywords: Atopic dermatitis; Chronic contact hypersensitivity; Cytokines; IgE; Toll like receptor 3.

MeSH terms

  • Animals
  • Chronic Disease
  • Cytokines / metabolism
  • Dermatitis, Allergic Contact / blood
  • Dermatitis, Allergic Contact / immunology*
  • Disease Models, Animal
  • Humans
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Leukocytes / immunology
  • Leukocytes / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Oxazolone / immunology
  • Picryl Chloride / immunology
  • Signal Transduction / immunology*
  • Skin / cytology
  • Skin / immunology*
  • Toll-Like Receptor 3 / genetics
  • Toll-Like Receptor 3 / immunology*
  • Toll-Like Receptor 3 / metabolism


  • Cytokines
  • TLR3 protein, mouse
  • Toll-Like Receptor 3
  • Oxazolone
  • Immunoglobulin E
  • Picryl Chloride