徳島大学 教育・研究者情報データベース(EDB)

1. (英) Okamoto Masakazu

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2. (英) Matsuda Hiroyuki

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3. (英) Joetham Anthony

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4. (英) Lucas J. Joseph

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5. (英) Domenico Joanne

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6. 安友 康二([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.病理系.生体防御医学])

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7. (英) Takeda Katsuyuki

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8. (英) Gelfand W. Erwin

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(英) Jagged1 on dendritic cells and Notch on CD4+ T cells initiate lung allergic responsiveness by inducing IL-4 production.

(英) Jagged1, a Notch ligand, and Notch have been implicated in Th2 differentiation, but their role in initiating IL-4 production and Th2 differentiation in vivo and the development of allergic airway responses has not been defined. In this study, we show that Jagged1 is up-regulated on bone marrow-derived dendritic cells (BMDCs) pulsed with allergen and that the transfer of these BMDCs before allergen challenge induces airway hyperresponsiveness (AHR) and eosinophilic airway inflammation. Treatment of CD4(+) T cells with a gamma-secretase inhibitor (GSI), which inhibits Notch signaling, resulted in decreased cytokine production when the cells were cocultured with allergen-pulsed, Jagged1-expressing BMDCs and, after the transfer of allergen-pulsed BMDCs, IL-4-deficient (IL-4(-/-)) recipients of GSI-treated naive CD4(+) T cells developed lower levels of AHR, reduced numbers of eosinophils, and lower Th2 cytokine levels when challenged with allergen. In vivo treatment of wild-type mice with Jagged1-Fc enhanced AHR and airway inflammation, whereas the transfer of BMDC transfected with Jagged1 small interfering RNA (siRNA) cells into WT or IL-4(-/-) mice before transfer of CD4(+) T cells resulted in decreased AHR, inflammation, and Th2 cytokines, indicating the critical role for Jagged1 expression on APCs. These data identify the essential role of the interactions between Notch on CD4(+) T cells and Jagged1 on APCs in the initiation of IL-4 production and Th2 differentiation for the development of AHR and allergic airway inflammation.

1. (英) Animals
2. (英) Bronchial Hyperreactivity
3. (英) CD4-Positive T-Lymphocytes
4. (英) Calcium-Binding Proteins
5. (英) Cells, Cultured
6. (英) Coculture Techniques
7. (英) Dendritic Cells
8. (英) Eosinophilia
9. (英) Female
10. (英) Inflammation Mediators
11. (英) Intercellular Signaling Peptides and Proteins
12. (英) Interleukin-4
13. (英) Lung
14. (英) Male
15. (英) Membrane Proteins
16. (英) Mice
17. (英) Mice, Inbred C57BL
18. (英) Mice, Knockout
19. (英) Ovalbumin
20. (英) Receptors, Notch
21. (英) Th2 Cells

1. (英) Article.Affiliation: Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, CO 80206, USA.

2. (英) Article.PublicationTypeList.PublicationType: Journal Article

3. (英) Article.PublicationTypeList.PublicationType: Research Support, N.I.H., Extramural