TH2 dominance and defective development of a CD8+ dendritic cell subset in Id2-deficient mice
Copyright policy )TH2 dominance and defective development of a CD8+ dendritic cell subset in Id2-deficient mice
Although the TH1/TH2 balance is important in many clinical situations, the regulatory mechanisms in vivo have not been well elucidated.We sought to characterize the immunologic status of mice lacking Id2, an inhibitor of basic helix-loop-helix transcription factors.We analyzed serum immunoglobulin levels, gene-expression profiles in the spleen, TH1/TH2 balance, and dendritic cell (DC) populations of Id2-/- mice.Serum levels of TH2-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 TH2-related genes, such as IL-4, and reduced expression of TH1-related genes, including IFN-gamma and IL-12. Intracellular cytokine staining also confirmed that Id2-/- splenic CD4+ T cells are substantially skewed to TH2 cells. However, Id2-/- naive CD4+ T cells differentiated into TH1 cells comparably with wild-type T cells under the appropriate culture conditions. Id2-/- mice displayed a selective and remarkable reduction of the CD8+ DC subset, which is known to induce preferential TH1 differentiation.Id2 is an indispensable regulator of the TH1/TH2 balance, possibly through the proper development of CD8alpha+ DCs, and could be a novel target to treat allergic diseases.
- Kyoto University Japan
CD4-Positive T-Lymphocytes, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression, Cell Differentiation, Dendritic Cells, CD8-Positive T-Lymphocytes, Mice, Mutant Strains, DNA-Binding Proteins, Repressor Proteins, Mice, Th2 Cells, T-Lymphocyte Subsets, Animals, Cell Division, Spleen, Inhibitor of Differentiation Protein 2, Transcription Factors
CD4-Positive T-Lymphocytes, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression, Cell Differentiation, Dendritic Cells, CD8-Positive T-Lymphocytes, Mice, Mutant Strains, DNA-Binding Proteins, Repressor Proteins, Mice, Th2 Cells, T-Lymphocyte Subsets, Animals, Cell Division, Spleen, Inhibitor of Differentiation Protein 2, Transcription Factors
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