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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-...

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Detalles Bibliográficos
Autores principales: Hodgson, Rose, Xu, Xijin, Anzilotti, Consuelo, Deobagkar-Lele, Mukta, Crockford, Tanya L., Kepple, Jessica D., Cawthorne, Eleanor, Bhandari, Aneesha, Cebrian-Serrano, Alberto, Wilcock, Martin J., Davies, Benjamin, Cornall, Richard J., Bull, Katherine R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9649591/
https://www.ncbi.nlm.nih.gov/pubmed/36357486
http://dx.doi.org/10.1038/s42003-022-04118-w
Descripción
Sumario: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 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(−/−) 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.