| First Author | Hodgson R | Year | 2022 |
| Journal | Commun Biol | Volume | 5 |
| Issue | 1 | Pages | 1216 |
| PubMed ID | 36357486 | Mgi Jnum | J:334179 |
| Mgi Id | MGI:7385426 | Doi | 10.1038/s42003-022-04118-w |
| Citation | Hodgson R, et al. (2022) NDRG1 is induced by antigen-receptor signaling but dispensable for B and T cell self-tolerance. Commun Biol 5(1):1216 |
| abstractText | 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(+) T cell clonal anergy factor. By RNA-sequencing, we identified Ndrg1 as the third most upregulated gene in anergic, compared to naive 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(-/-) 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(+) T cells, demonstrating that NDGR1 is functionally redundant for lymphocyte anergy. |
