This study examined the role of CASTOR1 (an arginine sensor that regulates mTORC1) in humoral immunity and SLE pathogenesis, using transcriptomic data from B cell subsets in SLE patients (n=129 primary analysis) and both global and B cell-specific Castor1-deficient mouse models.
CASTOR1 expression in plasmablasts was inversely correlated with SLE disease activity (SLEDAI-2K; r = −0.32, p = 0.00031). Castor1-deficient mice developed elevated serum IgG, anti-dsDNA antibodies, expanded plasma cell populations in spleen and bone marrow, and IgG-deposit glomerulonephritis — an SLE-like phenotype replicated in B cell-specific knockouts, pointing to a B cell-intrinsic mechanism.
Transcriptomic findings are correlational and from bulk RNA sequencing, limiting cell-level resolution. Mouse knockout models may not fully recapitulate human SLE pathophysiology. Full-text access was unavailable, so mechanistic details and confounding factors cannot be fully assessed.
CASTOR1 appears to restrain plasma cell expansion and autoantibody production via mTORC1 signaling in B cells, making it a candidate therapeutic target in SLE. No clinical interventions are yet available, but this pathway warrants attention as mTOR-modulating strategies are explored in autoimmune disease.
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