PMID- 23188082
OWN - NLM
STAT- MEDLINE
DCOM- 20130314
LR  - 20211021
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 32
IP  - 1
DP  - 2013 Jan 9
TI  - The alarmin Mrp8/14 as regulator of the adaptive immune response during allergic 
      contact dermatitis.
PG  - 100-11
LID - 10.1038/emboj.2012.309 [doi]
AB  - 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.
FAU - Petersen, Beatrix
AU  - Petersen B
AD  - Institute of Immunology, University of Munster, Munster, Germany.
FAU - Wolf, Marc
AU  - Wolf M
FAU - Austermann, Judith
AU  - Austermann J
FAU - van Lent, Peter
AU  - van Lent P
FAU - Foell, Dirk
AU  - Foell D
FAU - Ahlmann, Martina
AU  - Ahlmann M
FAU - Kupas, Verena
AU  - Kupas V
FAU - Loser, Karin
AU  - Loser K
FAU - Sorg, Clemens
AU  - Sorg C
FAU - Roth, Johannes
AU  - Roth J
FAU - Vogl, Thomas
AU  - Vogl T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121127
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Calgranulin A)
RN  - 0 (Calgranulin B)
RN  - 0 (Cytokines)
RN  - 0 (Leukocyte L1 Antigen Complex)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Adaptive Immunity
MH  - Animals
MH  - Antigen Presentation
MH  - Calgranulin A/blood/genetics/immunology/*metabolism
MH  - Calgranulin B/blood/genetics/immunology/*metabolism
MH  - Cell Communication
MH  - Cell Differentiation
MH  - Cell Proliferation
MH  - Cytokines/metabolism
MH  - Dendritic Cells/immunology/metabolism
MH  - Dermatitis, Allergic Contact/*immunology/metabolism
MH  - Ear/pathology
MH  - Leukocyte L1 Antigen Complex/*immunology/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Phenotype
MH  - Time-Lapse Imaging
MH  - Toll-Like Receptor 4/*immunology/metabolism
PMC - PMC3545303
COIS- The authors declare that they have no conflict of interest.
EDAT- 2012/11/29 06:00
MHDA- 2013/03/15 06:00
PMCR- 2014/01/09
CRDT- 2012/11/29 06:00
PHST- 2012/04/26 00:00 [received]
PHST- 2012/10/29 00:00 [accepted]
PHST- 2012/11/29 06:00 [entrez]
PHST- 2012/11/29 06:00 [pubmed]
PHST- 2013/03/15 06:00 [medline]
PHST- 2014/01/09 00:00 [pmc-release]
AID - emboj2012309 [pii]
AID - 10.1038/emboj.2012.309 [doi]
PST - ppublish
SO  - EMBO J. 2013 Jan 9;32(1):100-11. doi: 10.1038/emboj.2012.309. Epub 2012 Nov 27.