2003年1月
T(H)2 dominance and defective development of a CD8(+) dendritic cell subset in Id2-deficient mice
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
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- 巻
- 111
- 号
- 1
- 開始ページ
- 136
- 終了ページ
- 142
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1067/mai.2003.29
- 出版者・発行元
- MOSBY, INC
Background: Although the T(H)1/T(H)2 balance is important in many clinical situations, the regulatory mechanisms in vivo have not been well elucidated.
Objective: We sought to characterize the immunologic status of mice lacking Id2, an inhibitor of basic helix-loop-helix transcription factors.
Methods: We analyzed serum immunoglobulin levels, gene-expression profiles in the spleen, T(H)1/T(H)2 balance, and dendritic cell (DC) populations of Id2(-/-) mice.
Results: Serum levels of T(H)2-mediated IgG1 and IgE were increased more than 10-fold in Id2(-/-) mice without antigenic stimulation. Gene-expression analysis in Id2(-/-) splenocytes revealed enhanced expression of T(H)2-related genes, such as IL-4, and reduced expression of T(H)1-related genes, including IFN-gamma and IL-12. Intracellular cytokine staining also confirmed that Id2(-/-) splenic CD4(+) T cells are substantially skewed to T(H)2 cells. However, Id2(-/-) naive CD4(+) T cells differentiated into T(H)1 cells comparably with wild-type T cells under the appropriate culture conditions. Id2(-/-) mice displayed a selective and remarkable reduction of the CD8alpha(+)DC subset,which is known to induce preferential T(H)1 differentiation.
Conclusion: Id2 is an indispensable regulator of the T(H)1/T(H)2 balance, possibly through the proper development of CD8alpha(+) DCs, and could be a novel target to treat allergic diseases.
Objective: We sought to characterize the immunologic status of mice lacking Id2, an inhibitor of basic helix-loop-helix transcription factors.
Methods: We analyzed serum immunoglobulin levels, gene-expression profiles in the spleen, T(H)1/T(H)2 balance, and dendritic cell (DC) populations of Id2(-/-) mice.
Results: Serum levels of T(H)2-mediated IgG1 and IgE were increased more than 10-fold in Id2(-/-) mice without antigenic stimulation. Gene-expression analysis in Id2(-/-) splenocytes revealed enhanced expression of T(H)2-related genes, such as IL-4, and reduced expression of T(H)1-related genes, including IFN-gamma and IL-12. Intracellular cytokine staining also confirmed that Id2(-/-) splenic CD4(+) T cells are substantially skewed to T(H)2 cells. However, Id2(-/-) naive CD4(+) T cells differentiated into T(H)1 cells comparably with wild-type T cells under the appropriate culture conditions. Id2(-/-) mice displayed a selective and remarkable reduction of the CD8alpha(+)DC subset,which is known to induce preferential T(H)1 differentiation.
Conclusion: Id2 is an indispensable regulator of the T(H)1/T(H)2 balance, possibly through the proper development of CD8alpha(+) DCs, and could be a novel target to treat allergic diseases.
- リンク情報
- ID情報
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- DOI : 10.1067/mai.2003.29
- ISSN : 0091-6749
- PubMed ID : 12532109
- Web of Science ID : WOS:000180465500021