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Transcriptional profiling identifies Id2 function in dendritic cell development

Nature Immunology volume 4, pages 380–386 (2003)Cite this article

Abstract

Dendritic cells (DCs) are potent antigen-presenting cells with a pivotal role in antigen-specific immune responses. Here, we found that the helix-loop-helix transcription factor Id2 is up-regulated during DC development in vitro and crucial for the development of distinct DC subsets in vivo. Id2−/− mice lack Langerhans cells (LCs), the cutaneous contingent of DCs, and the splenic CD8α+ DC subset is markedly reduced. Mice deficient for transforming growth factor (TGF)-β also lack LCs, and we demonstrate here that, in DCs, TGF-β induces Id2 expression. We also show that Id2 represses B cell genes in DCs. These findings reveal a TGF-β–Id2 signaling pathway in DCs and suggest a mechanism by which Id2 affects the lineage choice of B cell and DC progenitors.

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Figure 1: Differentiation of human DCs from hematopoietic progenitor cells in vitro.
Figure 2: RNA hybridization and immunoblot analysis of Id2 expression in human and mouse DCs.
Figure 3: Id2−/− mice lack CD8α+ DCs and LCs.
Figure 4: TGF-β induces Id2 transcription.

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Acknowledgements

We thank F. Sablitzky for Id1 and Id2 cDNA; S. Saeland for the langerin antibody; D. Kobelt and A. Steinkasserer for HSV; H.D. Klenk for influenza virus; A. Mansouri and P. Gruss for sharing the Id2−/− mice; P. Grasshoff, T. Kaiser and K. Raba for cell sorting; S.S. Diebold and T. Blankenstein for discussions and support; S. Knespel and G. Blendinger for technical assistance; and P. Haink and P. Podlatis for secretarial assistance. This work was funded by grants of the Fonds der Chemischen Industrie, German Research Foundation (Ze 432/1 and Ze432/2) to M.Z. and a grant of the Edward Jenner Institute for Vaccine Research to M.Z. and T.C.G. X.-S.J. received a postdoctoral fellowship from the German Academic Exchange Service.

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Author notes

  1. Christiane Kuhl

    Present address: Weatherall Institute of Molecular Medicine, Headington, Oxford, OX3 9DS, UK

  2. Christine Hacker and Ralf D. Kirsch: These authors contributed equally to this work.

Authors and Affiliations

  1. Max-Delbrück-Center for Molecular Medicine, MDC, Robert-Rössle-Str. 10, Berlin, 13092, Germany

    Christine Hacker, Ralf D. Kirsch, Xin-Sheng Ju, Thomas Hieronymus, Tatjana C. Gust, Christiane Kuhl, Thorsten Jorgas, Steffen M. Kurz & Martin Zenke

  2. Department of Biochemistry, Christian-Albrechts-University, Olshausenstr. 40, Kiel, 24098, Germany

    Stefan Rose-John

  3. Department of Biochemistry, Fukui Medical University, Matsuoka, Fukui, 910-1193, Japan

    Yoshifumi Yokota

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Hacker, C., Kirsch, R., Ju, XS. et al. Transcriptional profiling identifies Id2 function in dendritic cell development. Nat Immunol 4, 380–386 (2003). https://doi.org/10.1038/ni903

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