Lactate bridges mesangial cells to the differentiation of follicular helper T cells in lupus nephritis.

ABSTRACT: Lupus nephritis (LN), a serious complication of systemic lupus erythematosus, is characterized by the deposition of IgG immune complexes. The generation of these autoantibodies depends on T follicular helper (Tfh) cells within secondary lymphoid organs. However, the potential contribution of Tfh cells residing within the kidney has remained unexplored. Here, our analysis of a single-cell kidney dataset from LN patients, alongside studies in humanized chimeras and kidney organoids, identifies the accumulation of renal Tfh cells. Mechanistically, self-DNA-stimulated LN-associated mesangial cells (MC) promote Tfh differentiation by inducing CNBP-mediated MPC1 deficiency, leading to increased lactate production. In turn, elevated lactate levels enhance PCAF-catalyzed BCL6 lactylation and subse

SUBMITTER: Liu M 

PROVIDER: S-EPMC12816631 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature