Arthritis & rheumatology (Hoboken, N.J.)
September 4, 2026 · via Europe PMC
CASTOR1 Regulates Humoral Immune Responses and Contributes to the Pathogenesis of Systemic Lupus Erythematosus.
Kusuda T, Komai T, Itamiya T, Abe T, Okamura T, Fujio K.
AI summary — for doctors, generated from the abstract only
In mice, loss of a metabolic sensor protein called CASTOR1 in B cells caused lupus-like autoimmune disease (excess antibody production, kidney inflammation), and in human lupus patients, lower CASTOR1 levels in antibody-producing cells correlated with higher disease activity, suggesting CASTOR1 as a potential new therapeutic target.
What was studied
A study combining human B-cell transcriptome analysis (136 SLE patients, 129 in primary analysis) with mouse models (whole-body and B-cell-specific Castor1-deficient mice) to investigate the role of CASTOR1, an arginine-sensing regulator of mTORC1 signaling, in humoral immune responses and lupus pathogenesis.
Key findings
- CASTOR1 expression in plasmablasts was inversely correlated with SLE disease activity (SLEDAI-2K) in human patients (r=-0.32, p=0.00031).
- Castor1-deficient mice showed increased plasma cell populations in spleen and bone marrow, elevated serum IgG, production of anti-double-stranded DNA antibodies, and glomerulonephritis with IgG deposits—features resembling SLE-like autoimmunity.
- B-cell-specific Castor1-deficient mice also showed increased plasma cell counts, elevated serum IgG, and glomerulonephritis, indicating CASTOR1 regulates systemic humoral immunity through a B-cell-intrinsic mechanism.
Clinical relevance
The findings suggest CASTOR1 plays a regulatory role in preventing excessive antibody-producing cell activity, and that its reduced expression may contribute to lupus pathogenesis, representing a potential new therapeutic target for SLE, but this is primarily preclinical mouse research paired with correlative human gene expression data, not evidence of a tested human therapy.
Who should care
Limitations
The causal mouse model findings (Castor1 knockout) have not been tested as a therapeutic intervention in human lupus patients; the human data show correlation between CASTOR1 expression and disease activity but cannot establish causation in humans.
A newly identified metabolic regulator protein (CASTOR1) appears to control antibody-producing cell activity, and its loss causes lupus-like disease in mice while lower levels correlate with higher disease activity in human lupus patients, suggesting a potential new drug target.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
Abstract
Objective
CASTOR1 senses arginine and regulates mammalian target of rapamycin complex 1 (mTORC1), a central metabolic signaling molecule. This study aimed to elucidate the roles of CASTOR1 in humoral immune responses.
Methods
We analyzed human B cell transcriptomes from healthy controls and patients with systemic lupus erythematosus (SLE) via correlation analysis and gene set variation analysis using our database, Immune Cell Gene Expression Atlas from the University of Tokyo. Castor1-deficient and B cell-specific Castor1-deficient mice were used for analyses of serum immunoglobulins and autoantibodies, urinary proteins, renal pathology, gene expression, and flow cytometry in spleen and bone marrow cells. The culture supernatant of splenic B cells was used for immunoglobulin (Ig) analysis.
Results
Transcriptomic analysis of bulk RNA sequencing data from various B cell subsets in patients with SLE (n = 136; n = 129 included in the primary analysis) revealed a correlation between CASTOR1 expression and disease activity, with CASTOR1 expression in plasmablasts inversely correlated with Systemic Lupus Erythematosus Disease Activity Index 2000 (r = -0.32, P = 0.00031). Castor1-deficient mice exhibited increased plasma cell populations in the spleen and bone marrow, elevated serum IgG levels, production of anti-double-stranded DNA antibodies, and glomerulonephritis with IgG deposits, reflecting SLE-like autoimmunity. Moreover, B cell-specific Castor1-deficient mice showed increased plasma cell counts, elevated serum IgG levels, and glomerulonephritis, indicating that Castor1 might regulate systemic humoral immunity via a B cell-intrinsic mechanism.
Conclusion
CASTOR1 plays a regulatory role in humoral immunity and may contribute to the pathogenesis of autoimmune diseases such as SLE, representing a potential therapeutic target.
DOI
10.1002/art.70314
PMID
42695806
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
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