ArticleThe Journal of allergy and clinical immunology2020
Treatment with rapamycin can restore regulatory T-cell function in IPEX patients.
Article in The Journal of allergy and clinical immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05241444 (Phase 1 Study of Autologous CD4^LVFOXP3 in Participants With Immune Dysregulation Polyendocrinopathy Enteropathy X-linked), which is not on this map. Cited by 47 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase 1 Study of Autologous CD4^LVFOXP3 in Participants With Immune Dysregulation Polyendocrinopathy Enteropathy X-linked (IPEX) Syndrome
Who cites it
47 citing papers in PubMed, 70 citations in OpenAlex.
- Selective impact on regulatory T cells with sustained functional phenotypes by the interleukin-2 mutein VIS171 in a nonhuman primate model.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026Article
- Allogeneic hematopoietic cell transplantation for partial RAG deficiency in children and adults: Excellent outcomes with a reduced-intensity posttransplantation cyclophosphamide-based approach.The Journal of allergy and clinical immunology · 2026Article
- Clinical Spectrum and Therapeutic Options in Monogenic CTLA-4-, LRBA-, or SOCS1-Related Primary Immune Regulatory Disorders.The journal of allergy and clinical immunology. In practice · 2026Review
- Refractory infantile IPEX with Treg-restricted FOXP3null expression caused by a novel variant inJournal of human immunity · 2026Article
- CAR Treg therapies for neurodegenerative diseases.iScience · 2026Review
- Pediatric IPEX-Associated Dermatitis Responds To Dupilumab: Evidence from Skin Transcriptomics and Immune Profiling.Journal of clinical immunology · 2026Article
- Regulatory T cells in the era of cell and gene therapy: biology, clinical translation, and future prospects.Frontiers in immunology · 2026Review
- The dual role of T cells in solid organ transplant rejection and immune tolerance.Frontiers in immunology · 2026Review
- Lipid Metabolism in Regulatory T Cells in Health and Disease.Journal of inflammation research · 2026Review
- Targeting Inflammation-Oxidative Stress Crosstalk: Advances and Challenges in Nanocarrier-Based Interventional Strategies for Pulmonary Arterial Hypertension.International journal of nanomedicine · 2026Review
- Inborn errors of regulatory T-cell differentiation and function.The Journal of allergy and clinical immunology · 2025Review
- Transient rapamycin treatment avoids unwanted host immune responses toward AAV-delivered anti-HIV antibodies.Nature communications · 2025Article
- Inborn errors of immunity (primary immunodeficiencies).Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2025Review
- The 'TNature reviews. Rheumatology · 2025Review
- Sirolimus alleviated intractable diarrhea of IPEX syndrome: a case report and literature review.BMC pediatrics · 2024Review
- The dichotomic role of cytokines in aging.Biogerontology · 2024Review
- Comparison of emulsion and spray methods for fabrication of rapamycin-loaded acetalated dextran microparticles.RSC pharmaceutics · 2024Article
- TThe Journal of allergy and clinical immunology · 2024Review
- mTOR-mediated differentiation and maintenance of suppressive T cells at the center stage of IPEX treatment.Immunologic research · 2024Article
- Infections in Disorders of Immune Regulation.Pathogens (Basel, Switzerland) · 2024Review
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Authors and funding
23 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundImmune-dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a lethal disease caused by mutations in a transcription factor critical for the function of thymus-derived regulatory T (Treg) cells (ie, FOXP3), resulting in impaired Treg function and autoimmunity. At present, hematopoietic stem cell transplantation is the therapy of choice for patients with IPEX syndrome. If not available, multiple immunosuppressive regimens have been used with poor disease-free survival at long-term follow-up. Rapamycin has been shown to suppress peripheral T cells while sparing Treg cells expressing wild-type FOXP3, thereby proving beneficial in the clinical setting of immune dysregulation. However, the mechanisms of immunosuppression selective to Treg cells in patients with IPEX syndrome are unclear.
objectiveWe sought to determine the cellular and molecular basis of the clinical benefit observed under rapamycin treatment in 6 patients with IPEX syndrome with different FOXP3 mutations.
methodsPhenotype and function of FOXP3-mutated Treg cells from rapamycin-treated patients with IPEX syndrome were tested by flow cytometry and in vitro suppression assays, and the gene expression profile of rapamycin-conditioned Treg cells by droplet-digital PCR.
resultsClinical and histologic improvements in patients correlated with partially restored Treg function, independent of FOXP3 expression or Treg frequency. Expression of TNF-receptor-superfamily-member 18 (TNFRSF18, glucocorticoid-induced TNF-receptor-related) and EBV-induced-3 (EBI3, an IL-35 subunit) in patients' Treg cells increased during treatment as compared with that of Treg cells from untreated healthy subjects. Furthermore inhibition of glucocorticoid-induced TNF-receptor-related and Ebi3 partially reverted in vitro suppression by in vivo rapamycin-conditioned Treg cells.
conclusionsRapamycin is able to affect Treg suppressive function via a FOXP3-independent mechanism, thus sustaining the clinical improvement observed in patients with IPEX syndrome under rapamycin treatment.
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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.