NDRG1 is induced by antigen-receptor signaling but dispensable for B and T cell self-tolerance
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-...
| Hoofdauteurs: | , , , , , , , , , , , , |
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| Formaat: | Journal article |
| Taal: | English |
| Gepubliceerd in: |
Springer Nature
2022
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| _version_ | 1826313899182391296 |
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| author | Hodgson, R Xu, X Anzilotti, C Deobagkar-Lele, M Crockford, TL Kepple, JD Cawthorne, E Bhandari, A Cebrian-Serrano, A Wilcock, MJ Davies, B Cornall, RJ Bull, KR |
| author_facet | Hodgson, R Xu, X Anzilotti, C Deobagkar-Lele, M Crockford, TL Kepple, JD Cawthorne, E Bhandari, A Cebrian-Serrano, A Wilcock, MJ Davies, B Cornall, RJ Bull, KR |
| author_sort | Hodgson, R |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-09-25T04:23:39Z |
| format | Journal article |
| id | oxford-uuid:78d9604d-81ae-4a49-a1ab-c3de62b4bb7e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:23:39Z |
| publishDate | 2022 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:78d9604d-81ae-4a49-a1ab-c3de62b4bb7e2024-08-19T13:45:30ZNDRG1 is induced by antigen-receptor signaling but dispensable for B and T cell self-toleranceJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:78d9604d-81ae-4a49-a1ab-c3de62b4bb7eEnglishSymplectic ElementsSpringer Nature2022Hodgson, RXu, XAnzilotti, CDeobagkar-Lele, MCrockford, TLKepple, JDCawthorne, EBhandari, ACebrian-Serrano, AWilcock, MJDavies, BCornall, RJBull, KRPeripheral 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. |
| spellingShingle | Hodgson, R Xu, X Anzilotti, C Deobagkar-Lele, M Crockford, TL Kepple, JD Cawthorne, E Bhandari, A Cebrian-Serrano, A Wilcock, MJ Davies, B Cornall, RJ Bull, KR NDRG1 is induced by antigen-receptor signaling but dispensable for B and T cell self-tolerance |
| title | NDRG1 is induced by antigen-receptor signaling but dispensable for B and T cell self-tolerance |
| title_full | NDRG1 is induced by antigen-receptor signaling but dispensable for B and T cell self-tolerance |
| title_fullStr | NDRG1 is induced by antigen-receptor signaling but dispensable for B and T cell self-tolerance |
| title_full_unstemmed | NDRG1 is induced by antigen-receptor signaling but dispensable for B and T cell self-tolerance |
| title_short | NDRG1 is induced by antigen-receptor signaling but dispensable for B and T cell self-tolerance |
| title_sort | ndrg1 is induced by antigen receptor signaling but dispensable for b and t cell self tolerance |
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