Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 111, Issue 1, Pages 136-142Publisher
MOSBY, INC
DOI: 10.1067/mai.2003.29
Keywords
Id2; basic helix-loop-helix factor; T(H)1; T(H)2; dendtritic cell
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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.
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