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AbstractPeripheral 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 identifiedNdrg1as the third most upregulated gene in anergic, compared to naïve follicular, B cells.Ndrg1is 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, thoughNdrg1−/−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.

Original publication

DOI

10.1038/s42003-022-04118-w

Type

Journal article

Journal

Communications Biology

Publisher

Springer Science and Business Media LLC

Publication Date

10/11/2022

Volume

5