Basic and Clinical ImmunologyTH2 dominance and defective development of a CD8+ dendritic cell subset in Id2-deficient mice☆,☆☆,★
Section snippets
Mice
Id2 mutant mice20 were of the 129/Sv genetic background and were reared under specific pathogen-free conditions. Id2+/– mice displayed characteristics similar to those of wild-type litter mates in all experiments conducted unless otherwise specified. All animal procedures described in this study were performed in accordance with the guidelines for animal experiments of Kyoto University Graduate School of Medicine and Graduate School of Biostudies and Fukui Medical University.
Determination of serum levels of IgE and IgG subclasses
Total IgE and IgG
Increased serum levels of TH2-mediated immunoglobulins in Id2–/–mice
To evaluate the immunologic status of Id2–/– mice, we analyzed serum levels of IgE and IgG subclasses in Id2–/– mice by means of ELISA. The levels of IgE and IgG1 were substantially increased (by approximately 20-fold and 10-fold, respectively) in Id2–/– mice compared with those in control mice (Fig 1, A and B ).
Discussion
In this article we have shown that Id2–/– mice are in a TH2-dominant state and have a selective defect in the CD8+ DC subset. The TH2 dominance in the mutant mice was shown by examining serum immunoglobulin levels and verified with gene-expression analysis in the spleen and intracellular staining of cytokines in splenic CD4+ T cells. We initially speculated that Id2 regulates TH1/TH2 differentiation at the TH0 level as an intrinsic factor. However, purified naive CD4+ T cells of Id2–/– mice
Acknowledgements
We thank Dr S.-I. Nishikawa for helpful support and Dr T. Nishimura for suggestions.
References (41)
- et al.
Transcriptional regulation of Th1/Th2 polarization
Immunol Today
(2000) - et al.
Dendritic cell subsets and the regulation of Th1/Th2 responses
Semin Immunol
(2001) Isolation and characterization of plasmacytoid dendritic cells from Flt3 ligand and granulocyte-macrophage colony-stimulating factor-treated mice
Blood
(2001)- et al.
Differentiation of myeloid dendritic cells into CD8α-positive dendritic cells in vivo
Blood
(2000) - et al.
Development of thymic and splenic dendritic cell populations from different hemopoietic precursors
Blood
(2001) - et al.
Dendritic cell potentials of early lymphoid and myeloid progenitors
Blood
(2001) - et al.
Arias CF, Marín AR, et al. Origin and differentiation of dendritic cells
Trends Immunol
(2001) - et al.
A novel transcription factor, T-bet, directs Th1 lineage commitment
Cell
(2000) - et al.
Multiorgan inflammation and hematopoietic abnormalities in mice with a targeted disruption of RelB, a member of the NF-κB/Rel family
Cell
(1995) - et al.
RelB is essential for the development of myeloid-related CD8α– dendritic cells but not of lymphoid-related CD8α+ dendritic cells
Immunity
(1998)
PU.1 is required for myeloid-derived but not lymphoid-derived dendritic cells
Blood
Cell-autonomous defects in dendritic cell populations of Ikaros mutant mice point to a developmental relationship with the lymphoid lineage
Immunity
Childhood risk factors for atopy and the importance of early intervention
J Allergy Clin Immunol
Signaling and transcription in T helper development
Annu Rev Immunol
Dendritic cells and the control of immunity
Nature
Immunobiology of dendritic cells
Annu Rev Immunol
Dendritic cells in the T-cell areas of lymphoid organs
Immunol Rev
CD4 and CD8 expression by dendritic cell subtypes in mouse thymus and spleen
J Immunol
CD8α+ and CD8α– subclasses of dendritic cells direct the development of distinct T helper cells in vivo
J Exp Med
CD11c+B220+Gr-1+ cells in mouse lymph nodes and spleen display characteristics of plasmacytoid dendritic cells
J Exp Med
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2019, ImmunobiologyCitation Excerpt :It has been established that IRF8 can directly drive the progenitors into classic CD8α+ DCs by targeting Id2 and Batf3 (Jaiswal et al., 2013), (Jackson et al., 2011). In Id2−/− mice, it is shown that the percentage of splenic CD8α+ DCs is reduced (Hacker et al., 2003), (Kusunoki et al., 2003). However, another report has demonstrated that Id2 is not essential for the development of CD8α+ DCs (Seillet et al., 2013).
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Drs Kusunoki and Sugai contributed equally to this work.
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Supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology, Japan (T.K.: 13670799, K.I.: B14370075 and 13140202, A.S.: 12206046 and 13206035, Y.Y.: 13470034 and 13037016); the Novartis Foundation and Research Project Funds of Fukui Medical University (Y.Y.); and Special Coordination Funds for Promoting Science and Technology (K.I.).
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Reprint requests: Yoshifumi Yokota, MD, PhD, Department of Biochemistry, Fukui Medical University, 23-3 Shimoaizuki, Matsuoka, Fukui 910-1193, Japan.