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Essential, dose-dependent role for the transcription factor Gata3 in the development of IL-5 + and IL-13 + type 2 innate lymphoid cells

Open access
Klein Wolterink, Roel G. J., Serafini, Nicolas, van Nimwegen, Menno, Vosshenrich, Christian A. J., de Bruijn, Marjolein J. W., Fonseca Pereira, Diogo, Veiga Fernandes, Henrique, Hendriks, Rudi W., Di Santo, James P.·2013·Proceedings of the National Academy of Sciences

Abstract

Group 2 innate lymphoid cells (ILC2s; also called nuocytes, innate helper cells, or natural helper cells) provide protective immunity during helminth infection and play an important role in influenza-induced and allergic airway hyperreactivity. Whereas the transcription factor GATA binding protein 3 ( Gata3 ) is important for the production of IL-5 and -13 by ILC2s in response to IL-33 or -25 stimulation, it is not known whether Gata3 is required for ILC2 development from hematopoietic stem cells. Here, we show that chimeric mice generated with Gata3 -deficient fetal liver hematopoietic stem cells fail to develop systemically dispersed ILC2s. In these chimeric mice, in vivo administration of IL-33 or -25 fails to expand ILC2 numbers or to induce characteristic ILC2-dependent IL-5 or -13 production. Moreover, cell-intrinsic Gata3 expression is required for ILC2 development in vitro and in vivo. Using mutant and transgenic mice in which Gata3 gene copy number is altered, we show that ILC2 generation from common lymphoid progenitors, as well as ILC2 homeostasis and cytokine production, is regulated by Gata3 expression levels in a dose-dependent fashion. Collectively, these results identify Gata3 as a critical early regulator of ILC2 development, thereby extending the paradigm of Gata3 -dependent control of type 2 immunity to include both innate and adaptive lymphocytes.

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Metadata

Authors
Klein Wolterink, R. G. J., Serafini, N., van Nimwegen, M., Vosshenrich, C. A. J., de Bruijn, M. J. W., Fonseca Pereira, D., Veiga Fernandes, H., Hendriks, R. W., & Di Santo, J. P.
Venue
Proceedings of the National Academy of Sciences
Published
2013-06-03
Volume
110
Issue
25
Pages
10240-10245
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W1990121282
Cited by
226
References
10
FWCI
14.32
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Essential, dose-dependent role for the transcription factor Gata3 in the development of IL-5 + and IL-13 + type 2 innate lymphoid cells. https://app.cochat.ai/papers/10.1073/pnas.1217158110
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Klein Wolterink, R. G. J., Serafini, N., van Nimwegen, M., Vosshenrich, C. A. J., de Bruijn, M. J. W., Fonseca Pereira, D., Veiga Fernandes, H., Hendriks, R. W., & Di Santo, J. P. (2013). Essential, dose-dependent role for the transcription factor Gata3 in the development of IL-5 + and IL-13 + type 2 innate lymphoid cells. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1217158110

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.