Toll-like receptor 2 ligands promote chronic atopic dermatitis through IL-4-mediated suppression of IL-10

63Citations
Citations of this article
66Readers
Mendeley users who have this article in their library.

Abstract

Background Atopic dermatitis (AD) is a T cell-mediated inflammatory skin disease, with TH2 cells initiating acute flares. This inflamed skin is immediately colonized with Staphylococcus aureus, which provides potent Toll-like receptor (TLR) 2 ligands. However, the effect of TLR2 ligands on the development of TH2-mediated AD inflammation remains unclear. Objective We investigated the progression of TH2 cell-mediated dermatitis after TLR2 activation. Methods Using models for acute AD with T H2 cells initiating cutaneous inflammation, we investigated the consequences of TLR2 activation. Dermatitis, as assessed by changes in ear skin thickness and histology, was analyzed in different BALB/c and C57BL/6 wild-type and knockout mouse strains, and immune profiling was carried out by using in vitro and ex vivo cytokine analyses. Results We show that TH2 cell-mediated dermatitis is self-limiting and depends on IL-4. Activation of TLR2 converted the limited TH2 dermatitis to chronic cutaneous inflammation. We demonstrate that the concerted activation of TLR2 and IL-4 receptor on dendritic cells is sufficient for this conversion. As an underlying mechanism, we found that the combinatorial sensing of the innate TLR2 ligands and the adaptive TH2 cytokine IL-4 suppressed anti-inflammatory IL-10 and consequently led to the exacerbation and persistence of dermatitis. Conclusion Our data demonstrate that innate TLR2 signals convert transient TH2 cell-mediated dermatitis into persistent inflammation, as seen in chronic human AD, through IL-4-mediated suppression of IL-10. For the first time, these data show how initial AD lesions convert to chronic inflammation and provide another rationale for targeting IL-4 in patients with AD, a therapeutic approach that is currently under development. © 2014 American Academy of Allergy, Asthma and Immunology.

Cite

CITATION STYLE

APA

Kaesler, S., Volz, T., Skabytska, Y., Köberle, M., Hein, U., Chen, K. M., … Biedermann, T. (2014). Toll-like receptor 2 ligands promote chronic atopic dermatitis through IL-4-mediated suppression of IL-10. Journal of Allergy and Clinical Immunology, 134(1). https://doi.org/10.1016/j.jaci.2014.02.017

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free