2005 Fiscal Year Final Research Report Summary
Analysis of mechanisms for counter-regulation between TLR and FcεRI using model mice for atopic dermatitis
| Project/Area Number |
16591117
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Kyorin University School of Medicine |
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Principal Investigator |
HAYAKAWA Jun Kyorin University School of Medicine, Department of Dermatology, assistant, 医学部, 助手 (30255393)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUKAWA Yoshiko Kyorin University School of Medicine, Department of Dermatology, assistant, 医学部, 助手 (50301479)
TAKAHASHI Ryo Kyorin University School of Medicine, Department of Dermatology, assistant, 医学部, 助手 (00317091)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Toll-like receptor / mast cell / immediate-type hypersensitivity / FcεRI / late phase reaction |
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| Research Abstract |
In this study, we asked whether IgE, which is traditionally considered to have a central role in eliciting immediate-type hypersensitivity (ITH) reactions in allergic diseases, can play an important role in regulating innate immune responses. We found that Toll-like receptor (TLR)2-dependent rapid footpad swelling corresponding to ITH is elicited after hapten exposure to the footpad. This TLR2-dependent ITH is mediated by mast cell degranulation and can be inhibited by hapten-specific IgE. In contrast, such IgE is essential for hapten-specific ITH induced in the ear repeatedly exposed to the hapten. This inhibitory role of hapten-specific IgE in TLR2-dependent mast cell activation is also observed in mast cell knock-in mice reconstituted with bone marrow-derived mast cells (BMMCs) from wild type, but not TLR2^<-/-> mice. The inhibition of TLR2-dependent mast cell activation by IgE is only observed when BMMCs are pretreated with IgE specific for the exposed hapten at appropriate concentrations. These findings indicate that IgE might not always be detrimental to the host but, under some circumstances, have a key role in counter-regulating certain aspects of innate immunity. IgE would represent a normal physiological mechanism by which a tissue could downregulate an excessive destructive innate immune response.
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