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-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. CONCLUSION: 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.
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-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. CONCLUSION: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.
Authors: Liat Bar-On; Tal Birnberg; Kanako L Lewis; Brian T Edelson; Dunja Bruder; Kai Hildner; Jan Buer; Kenneth M Murphy; Boris Reizis; Steffen Jung Journal: Proc Natl Acad Sci U S A Date: 2010-08-02 Impact factor: 11.205
Authors: Yen-Yu Lin; Mary E Jones-Mason; Makoto Inoue; Anna Lasorella; Antonio Iavarone; Qi-Jing Li; Mari L Shinohara; Yuan Zhuang Journal: J Immunol Date: 2012-06-27 Impact factor: 5.422
Authors: Brian T Edelson; Wumesh KC; Richard Juang; Masako Kohyama; Loralyn A Benoit; Paul A Klekotka; Clara Moon; Jörn C Albring; Wataru Ise; Drew G Michael; Deepta Bhattacharya; Thaddeus S Stappenbeck; Michael J Holtzman; Sun-Sang J Sung; Theresa L Murphy; Kai Hildner; Kenneth M Murphy Journal: J Exp Med Date: 2010-03-29 Impact factor: 14.307