Dataset Information

The alarmin Mrp8/14 as regulator of the adaptive immune response during allergic contact dermatitis.

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.

SUBMITTER: Petersen B

PROVIDER: S-EPMC3545303 | biostudies-other | 2013 Jan

REPOSITORIES: biostudies-other

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The alarmin Mrp8/14 as regulator of the adaptive immune response during allergic contact dermatitis.

Petersen Beatrix B Wolf Marc M Austermann Judith J van Lent Peter P Foell Dirk D Ahlmann Martina M Kupas Verena V Loser Karin K Sorg Clemens C Roth Johannes J Vogl Thomas T

The EMBO journal 20121127 1

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 mat ...[more]

PMID: 23188082

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Project description:Genes involved in the inflammatory response resulting in allergic contact dermatitis (ACD) are only partly known. In this study, we introduce the use of high density oligonucleotide arrays for gene expression profiling in human skin during the elicitation of ACD. Skin biopsies from normal and nickel-exposed skin were obtained from 7 nickel-allergic patients and 5 non-allergic controls at four different time points during elicitation of eczema: 0h, 7h, 48h and 96h. Each gene expression profile was analysed by hybridization to high density oligonucletide arrays. Cluster analysis of 74 genes found to be differentially expressed in the patients over time revealed that the patient samples may be categorised into two groups: An early time point group (0h and 7h) and a late time point group (48h and 96h). Compared to the early time points, late time point skin samples were characterised by the up-regulation of inflammatory molecules including genes involved in the class I antigen presenting pathway and genes involved in lymphocyte adhesion and motility ; Correspondence analysis including both patients and controls revealed three distinct groups: i) the control group, ii) the early time point patient group (0h and 7h) and iii) the late time point patient group (48h and 96h). Experiment Overall Design: For the microarray study, 7 nickel-allergic patients and 5 non-allergic controls were recruited. All subjects were female. The skin covering the upper nates was exposed to nickel delivered during a patch test. Skin biopsies were taken to generate a time-series. Skin was exposed to nickel for 0h, 7h, 48h and 96h. Experiment Overall Design: All nickel allergic patients reacted with visible eczama at the 48h and 96h time-points. No eczema was vissible at the 0h or 7h time-points. Control subjects did not show visible eczema at any time-point. Experiment Overall Design: RNA was extracted from the skin biopsies and 34 biopsies yielded RNA of sufficient quantity and quality for micro-array analysis.

Dataset Information

The alarmin Mrp8/14 as regulator of the adaptive immune response during allergic contact dermatitis.

Publications

The alarmin Mrp8/14 as regulator of the adaptive immune response during allergic contact dermatitis.

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