Journal article
NDRG1 is induced by antigen-receptor signaling but dispensable for B and T cell self-tolerance
- Abstract:
- Peripheral tolerance prevents the initiation of damaging immune responses by autoreactive lymphocytes. While tolerogenic mechanisms are tightly regulated by antigen-dependent and independent signals, downstream pathways are incompletely understood. N-myc downstream-regulated gene 1 (NDRG1), an anti-cancer therapeutic target, has previously been implicated as a CD4<sup>+</sup> T cell clonal anergy factor. By RNA-sequencing, we identified Ndrg1 as the third most upregulated gene in anergic, compared to naïve follicular, B cells. Ndrg1 is upregulated by B cell receptor activation (signal one) and suppressed by co-stimulation (signal two), suggesting that NDRG1 may be important in B cell tolerance. However, though Ndrg1<sup>-/-</sup> mice have a neurological defect mimicking NDRG1-associated Charcot-Marie-Tooth (CMT4d) disease, primary and secondary immune responses were normal. We find that B cell tolerance is maintained, and NDRG1 does not play a role in downstream responses during re-stimulation of in vivo antigen-experienced CD4<sup>+</sup> T cells, demonstrating that NDGR1 is functionally redundant for lymphocyte anergy.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 2.7MB, Terms of use)
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- Publisher copy:
- 10.1038/s42003-022-04118-w
Authors
- Publisher:
- Springer Nature
- Journal:
- Communications Biology More from this journal
- Volume:
- 5
- Issue:
- 1
- Article number:
- 1216
- Place of publication:
- England
- Publication date:
- 2022-11-10
- Acceptance date:
- 2022-10-17
- DOI:
- EISSN:
-
2399-3642
- Pmid:
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36357486
- Language:
-
English
- Keywords:
- Pubs id:
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1304570
- Local pid:
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pubs:1304570
- Deposit date:
-
2024-05-13
Terms of use
- Copyright holder:
- Hodgson et al.
- Copyright date:
- 2022
- Rights statement:
- © The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
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