TH2 dominance and defective development of a CD8+ dendritic cell subset in Id2-deficient mice

Abstract

Background: Although the TH1/TH2 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, TH1/TH2 balance, and dendritic cell (DC) populations of Id2-/- mice. Results: 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-γ 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 CD8α+ DC subset, which is known to induce preferential TH1 differentiation. Conclusion: Id2 is an indispensable regulator of the TH1/TH2 balance, possibly through the proper development of CD8α+ DCs, and could be a novel target to treat allergic diseases.