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Xist Deletion in B Cells Results in Systemic Lupus Erythematosus Phenotypes

ABSTRACT: Systemic lupus erythematosus (SLE) is an autoimmune disease preferentially observed in females. X-linked gene expression in XX females is normalized to that of XY males by XChromosome Inactivation (XCI). However, B cells from female SLE patients and mouse models of SLE exhibit mislocalization of Xist RNA, a critical regulator of XCI, and aberrant expression of X-linked genes, suggesting that impairment of XCI may contribute to disease. Here, we find that a subset of female mice harboring a conditional deletion of Xist in B cells (“Xist cKO”) spontaneously develop SLE phenotypes, including expanded activated B cell subsets, diseasespecific autoantibodies, and glomerulonephritis. Moreover, pristane-induced SLE-like disease is more severe in Xist cKO mice. Activated B cells from Xist cKO mice with SLE phenotypes have increased expression of proinflammatory X-linked genes implicated in SLE. Together, this work indicates that impaired XCI maintenance in B cells directly contributes to the female-bias of SLE.

ORGANISM(S): Mus musculus

PROVIDER: GSE311313 | GEO | 2026/05/15

REPOSITORIES: GEO

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