The Alarmin Mrp8/14 As Regulator of the Adaptive Immune Response During Allergic Contact Dermatitis

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2012 Nov 29

PMID 23188082

Citations 31

Authors

Beatrix Petersen

Marc Wolf

Judith Austermann

Peter van Lent

Dirk Foell

Martina Ahlmann

Verena Kupas

Karin Loser

Clemens Sorg

Johannes Roth

Thomas Vogl

Affiliations

Soon will be listed here.

Abstract

Mrp8 and Mrp14 are endogenous alarmins amplifying inflammation via Toll-like receptor-4 (TLR-4) activation. Due to their pro-inflammatory properties, alarmins are supposed to enhance adaptive immunity via activation of dendritic cells (DCs). In contrast, analysing a model of allergic contact dermatitis (ACD) we observed a more severe disease outcome in Mrp8/14-deficient compared to wild-type mice. This unexpected phenotype was associated with an enhanced T-cell response due to an accelerated maturation of DCs in Mrp8/14-deficient mice. Accordingly, Mrp8, the active component of the heterocomplex, inhibits early DC maturation and antigen presentation in a TLR-4-dependent manner. Transfer of DCs purified from the local lymph nodes of sensitized Mrp8/14-deficient to wild-type mice determined the outcome of ACD. Our results link a pro-inflammatory role of the endogenous TLR-4 ligand Mrp8/14 to a regulatory function in adaptive immunity, which shows some similarities with the 'hygiene hypothesis' regarding continuous TLR-4 stimulation and decreased risk of allergy.

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