Inositol-Requiring Enzyme 1α-Mediated Synthesis of Monounsaturated Fatty Acids as a Driver of B Cell Differentiation and Lupus-like Autoimmune Disease.

ABSTRACT:

Objective

To explore the molecular mechanisms underlying dysregulation of lipid metabolism in the pathogenesis of systemic lupus erythematosus (SLE).

Methods

B cells in peripheral blood from patients with SLE and healthy controls were stained with BODIPY dye for detection of lipids. Mice with targeted knockout of genes for B cell-specific inositol-requiring enzyme 1α (IRE-1α) and stearoyl-coenzyme A desaturase 1 (SCD-1) were used for studying the influence of the IRE-1α/SCD-1/SCD-2 pathway on B cell differentiation and autoantibody production. The preclinical efficacy of IRE-1α suppression as a treatment for lupus was tested in MRL.Fas^lpr mice.

Results

In cultures with mouse IRE-1α-null B cells, supplementation with monounsaturated fatty acids largely rescu

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC8651829 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature