Up-regulation of proBDNF/p75^NTR signaling in antibody-secreting cells drives systemic lupus erythematosus.

ABSTRACT: Inappropriate expansion of antibody-secreting cells (ASCs) is typical of systemic lupus erythematosus (SLE), but the regulatory signaling of pathogenic ASCs is unclear. The present study shows that brain-derived neurotrophic factor precursor (proBDNF) and its high-affinity pan-75 neurotrophin receptor (p75^NTR) are highly expressed in CD19⁺CD27^hiCD38^hi ASCs in patients with SLE and in CD19⁺CD44^hiCD138⁺ ASCs in lupus-like mice. The increased proBDNF⁺ ASCs were positively correlated with clinical symptoms and higher titers of autoantibodies in SLE. Administration of monoclonal antibodies against proBDNF or specific knockout of p75^NTR in CD19⁺ B cells exerted a therapeutic effect on lu

SUBMITTER: Shen WY 

PROVIDER: S-EPMC8769540 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature