title: 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-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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kusunoki
authors.forename: Manabu
authors.initials: M
authors.lastname: Sugai
authors.forename: Tomoya
authors.initials: T
authors.lastname: Katakai
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Omatsu
authors.forename: Tomonori
authors.initials: T
authors.lastname: Iyoda
authors.forename: Kayo
authors.initials: K
authors.lastname: Inaba
authors.forename: Tatsutoshi
authors.initials: T
authors.lastname: Nakahata
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Yokota
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D015870:Gene Expression; D051797:Inhibitor of Differentiation Protein 2; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000166:cytology; D018418:Th2 Cells; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D012097:Repressor Proteins; D014157:Transcription Factors