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The transcription factor RelB restrains group 2 innate lymphoid cells and type 2 immune pathology in vivo

Cellular & Molecular Immunology volume 18, pages 230–242 (2021)Cite this article

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Abstract

The exact relationships between group 2 innate lymphoid cells (ILC2s) and Th2 cells in type 2 pathology, as well as the mechanisms that restrain the responses of these cells, remain poorly defined. Here we examined the roles of ILC2s and Th2 cells in type 2 lung pathology in vivo using germline and conditional Relb-deficient mice. We found that mice with germline deletion of Relb (Relb−/−) spontaneously developed prominent type 2 pathology in the lung, which contrasted sharply with mice with T-cell-specific Relb deletion (Relbf/fCd4-Cre), which were healthy with no observed autoimmune pathology. We also found that in contrast to wild-type B6 mice, Relb-deficient mice showed markedly expanded ILC2s but not ILC1s or ILC3s. Moreover, adoptive transfer of naive CD4+ T cells into Rag1−/−Relb−/− hosts induced prominent type 2 lung pathology, which was inhibited by depletion of ILC2s. Mechanistically, we showed that Relb deletion led to enhanced expression of Bcl11b, a key transcription factor for ILC2s. We concluded that RelB plays a critical role in restraining ILC2s, primarily by suppressing Bcl11b activity, and consequently inhibits type 2 lung pathology in vivo.

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Acknowledgements

We acknowledge the Flow Cytometry Core and the Pathology Core at Houston Methodist for excellent services. This work was supported in part by the National Institutes of Health (R01AI080779) and the Kleberg Foundation.

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Authors and Affiliations

  1. Immunobiology and Transplant Science Center, and Department of Surgery, Houston Methodist Hospital, Texas Medical Center, Houston, Texas, USA

    Lei Zhang, Yuanlin Ying, Shuqiu Chen, Preston R. Arnold, Xiang Xiao & Xian C. Li

  2. Department of Neurology, Xiangya Hospital, Central South University, Changsha, China

    Lei Zhang & Fafa Tian

  3. Department of Urology, Southeast University Zhongda Hospital, Nanjing, China

    Shuqiu Chen

  4. Department of Surgery, Weill Cornell Medical College of Cornell University, New York, NY, USA

    Xian C. Li

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  1. Lei Zhang
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Correspondence to Xian C. Li.

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Zhang, L., Ying, Y., Chen, S. et al. The transcription factor RelB restrains group 2 innate lymphoid cells and type 2 immune pathology in vivo. Cell Mol Immunol 18, 230–242 (2021). https://doi.org/10.1038/s41423-020-0404-0

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