title: 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.
authors.affiliation: Institute of Immunology, University of Münster, Münster, Germany.
authors.forename: Beatrix
authors.initials: B
authors.lastname: Petersen
authors.forename: Marc
authors.initials: M
authors.lastname: Wolf
authors.forename: Judith
authors.initials: J
authors.lastname: Austermann
authors.forename: Peter
authors.initials: P
authors.lastname: van Lent
authors.forename: Dirk
authors.initials: D
authors.lastname: Foell
authors.forename: Martina
authors.initials: M
authors.lastname: Ahlmann
authors.forename: Verena
authors.initials: V
authors.lastname: Kupas
authors.forename: Karin
authors.initials: K
authors.lastname: Loser
authors.forename: Clemens
authors.initials: C
authors.lastname: Sorg
authors.forename: Johannes
authors.initials: J
authors.lastname: Roth
authors.forename: Thomas
authors.initials: T
authors.lastname: Vogl
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D017951:Antigen Presentation; D040501:Calgranulin A / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D040502:Calgranulin B / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002450:Cell Communication; D002454:Cell Differentiation; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000378:metabolism; D004423:Ear / Q000473:pathology; D039841:Leukocyte L1 Antigen Complex / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D059008:Time-Lapse Imaging; D051197:Toll-Like Receptor 4 / Q000276:immunology* / Q000378:metabolism
chemical_list: D040501:Calgranulin A; D040502:Calgranulin B; D016207:Cytokines; D039841:Leukocyte L1 Antigen Complex; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4