ArticleThe Journal of clinical investigation2019
Splicing factor SRSF1 controls T cell hyperactivity and systemic autoimmunity.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.
- Serine and arginine rich splicing factor 1 deficiency alters pathways involved in IL-17A expression and is implicated in human psoriasis.Clinical immunology (Orlando, Fla.) · 2022Pooled it
- HnRNPA2B1 tunes antimycobacterial immune responses in macrophages through alternative splicing ofInfection and immunity · 2026Article
- Systemic lupus pregnancies are characterized by an intrinsic pro-inflammatory monocyte transcriptome, driven by an aberrant miRNA signature.Journal of translational autoimmunity · 2026Article
- HnRNPA2B1 tunes antimycobacterial immune responses in macrophages through alternative splicing ofbioRxiv : the preprint server for biology · 2025Article
- TEAMwork: Interplay of Post-Transcriptional Mechanisms, Epigenetics and Metabolism in (Auto-)Immunity.European journal of immunology · 2025Review
- Guardians of silence: transcriptional networks in T cell quiescence.Experimental & molecular medicine · 2025Review
- Single-cell RNA sequencing reveals the heterogeneity and regulatory modules of cell-specific RNA-binding proteins in patients with systemic lupus erythematosus.Biochemistry and biophysics reports · 2025Article
- Review
- Immunocyte lipid metabolic reprogramming: a novel pathway for targeted intervention in autoimmune diseases.Frontiers in immunology · 2025Review
- Tumor-promoting effect and tumor immunity of SRSFs.Frontiers in cell and developmental biology · 2025Review
- Flotillin-2 dampens T cell antigen sensitivity and functionality.JCI insight · 2024Article
- Metabolic regulation of the immune system in health and diseases: mechanisms and interventions.Signal transduction and targeted therapy · 2024Review
- Autoregulated splicing ofScience (New York, N.Y.) · 2024Article
- Severe lupus nephritis in a young adult with PTEN hamartoma tumour syndrome.BMJ case reports · 2024Article
- Function of serine/arginine-rich splicing factors in hematopoiesis and hematopoietic malignancies.Cancer cell international · 2024Review
- CLK2 mediates IκBα-independent early termination of NF-κB activation by inducing cytoplasmic redistribution and degradation.Nature communications · 2024Article
- Rab4A-directed endosome traffic shapes pro-inflammatory mitochondrial metabolism in T cells via mitophagy, CD98 expression, and kynurenine-sensitive mTOR activation.Nature communications · 2024Article
- Splicing factor SRSF1 is essential for homing of precursor spermatogonial stem cells in mice.eLife · 2024Article
- Epigenetic Dysregulation in the Pathogenesis of Systemic Lupus Erythematosus.International journal of molecular sciences · 2024Review
- RNA circuits and RNA-binding proteins in T cells.Trends in immunology · 2023Review
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
Abstract
Systemic lupus erythematosus (SLE) is a devastating autoimmune disease in which hyperactive T cells play a critical role. Understanding molecular mechanisms underlying the T cell hyperactivity will lead to identification of specific therapeutic targets. Serine/arginine-rich splicing factor 1 (SRSF1) is an essential RNA-binding protein that controls posttranscriptional gene expression. We have demonstrated that SRSF1 levels are aberrantly decreased in T cells from patients with SLE and that they correlate with severe disease, yet the role of SRSF1 in T cell physiology and autoimmune disease is largely unknown. Here we show that T cell-restricted Srsf1-deficient mice develop systemic autoimmunity and lupus-nephritis. Mice exhibit increased frequencies of activated/effector T cells producing proinflammatory cytokines, and an elevated T cell activation gene signature. Mechanistically, we noted increased activity of the mechanistic target of rapamycin (mTOR) pathway and reduced expression of its repressor PTEN. The mTOR complex 1 (mTORC1) inhibitor rapamycin suppressed proinflammatory cytokine production by T cells and alleviated autoimmunity in Srsf1-deficient mice. Of direct clinical relevance, PTEN levels correlated with SRSF1 in T cells from patients with SLE, and SRSF1 overexpression rescued PTEN and suppressed mTORC1 activation and proinflammatory cytokine production. Our studies reveal the role of a previously unrecognized molecule, SRSF1, in restraining T cell activation, averting the development of autoimmune disease, and acting as a potential therapeutic target for lupus.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.