期刊
EMBO JOURNAL
卷 32, 期 1, 页码 100-111出版社
WILEY
DOI: 10.1038/emboj.2012.309
关键词
adaptive immunity; alarmins; calprotectin; DC; Mrp8/14
资金
- Interdisciplinary Center of Clinical Research [Vo2/014/09, Ro2/004/10]
- Federal Ministry of Education and Research, Germany
- German Research Foundation (DFG) [CRC Transregio 128-A2, CRC 1009 B8, CRC 1009 B9]
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 hetero-complex, 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. The EMBO Journal (2013) 32, 100-111. doi:10.1038/emboj.2012.309; Published online 27 November 2012
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