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An essential function for the nuclear receptor RORγt in the generation of fetal lymphoid tissue inducer cells

Nature Immunology volume 5, pages 64–73 (2004)Cite this article

Abstract

Lymphoid tissue inducer (LTi) cells are associated with early development of lymph nodes and Peyer's patches. We show here that during fetal life the nuclear hormone receptor RORγt is expressed exclusively in and is required for the generation of LTi cells. RORγt+ LTi cells provide essential factors, among which lymphotoxin-α1β2 is necessary but not sufficient for activation of the mesenchyma in lymph node and Peyer's patch anlagen. This early LTi cell–mediated activation of lymph node and Peyer's patch mesenchyma forms the necessary platform for the subsequent development of mature lymphoid tissues.

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Figure 1: In the fetus, RORγt is exclusively expressed in LTi cells.
Figure 2: A specific absence of LTi cells in RORγt-deficient fetuses.
Figure 3: Lymph node and Peyer's patch anlagen have high expression of ICAM-1 and VCAM-1.
Figure 4: LTα1β2 is necessary but not sufficient for the induction of lymph node and Peyer's patch development by LTi cells.
Figure 5: LTi cells do not proliferate, but are recruited to lymph node and Peyer's patch anlagen.

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Acknowledgements

BLC- and Id2-deficient mice were from J. Cyster (University of California at San Francisco, California) and Y. Yokota (Fukui Medical University, Fukui, Japan), respectively. The fusion protein TNF-R-I–Ig and the mAb AF.H6 were from J. Browning (Biogen). We thank J. Cyster, J. Browning, T. Sparwasser, T. Soos and B. Albrecht for discussions and critical reading of the manuscript. Supported by Swiss National Science Foundation (G.E.) and Howard Hughes Medical Institute (D.R.L.).

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  1. Gérard Eberl

    Present address: Aaron Diamond AIDS Research Center, New York, New York, 10016, USA

Authors and Affiliations

  1. Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, 10016, New York, USA

    Gérard Eberl, Shana Marmon, Mary-Jean Sunshine & Dan R Littman

  2. Howard Hughes Medical Institute, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, 10016, New York, USA

    Mary-Jean Sunshine & Dan R Littman

  3. Department of Immunology, Biogen, Cambridge, 02142, Massachusetts, USA

    Paul D Rennert

  4. Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, 19104, Pennsylvania, USA

    Yongwon Choi

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Eberl, G., Marmon, S., Sunshine, MJ. et al. An essential function for the nuclear receptor RORγt in the generation of fetal lymphoid tissue inducer cells. Nat Immunol 5, 64–73 (2004). https://doi.org/10.1038/ni1022

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