2007 Fiscal Year Final Research Report Summary
Developmentoftherapies for autoimmune diseases by targeting B cellsignaling
| Project/Area Number |
18591239
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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 | Kanazawa University |
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Principal Investigator |
FUJIMOTO Manabu Kanazawa University, Graduate Shcool of Meclical Science, Associate Professor (90272591)
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| Project Period (FY) |
2006 – 2007
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| Keywords | SKIN BIOLOGY / AUTOIMMUNITY |
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| Research Abstract |
We assessed the role of the B cell-specific surface molecule CD19 on the development of CHS through examining CD19-deficient mice. CD19 is a member of the Ig superfamily expressed on B cells and follicular dendritic cells, and serves as a positive B-cell response regulator which defines signaling thresholds critical for B cell responses. Contact hypersensitivity (CHS) is a cutaneous immune reaction mediated mainly by Ag-specific effector T cells, and regarded as a model for Th1/Tc1-mediated inflammation, while recent reports have suggested pivotal roles of B cells in CHS. Although CD19-deficient mice are hyposensitive to a variety of transmembrane signals, CD19 loss resulted in increased and prolonged reaction of CHS, suggesting an inhibitory role of CD19 expression in the etiology of CHS. Adoptive transfer experiments revealed that CD19 expression in B cells is recipient mice was required for optimal suppression of CHS response, indicating its role in elicitation phase. Furthermore, spleen B-2 cells, especially marginal zone B cells, from wild type mice were able to normalize exaggerated CHS reactions in CD19-deficient mice. Thus, CD19 expression in B cells is critical for termination of CHS responses, possibly through the function of "regulatory B cells". This B cell subset was also capable for improving murine lupus manifestations.
We also assessed serum BAFF and chemokine levels in patieits with autoimmune bullous diseases, and examined BAFF roles in TSK mice, an animal model of systemic sclerosis.
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