ArticleThe Journal of clinical investigation2017
Tregs restrain dendritic cell autophagy to ameliorate autoimmunity.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
What it found
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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.
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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.
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Who cites it
73 citing papers in PubMed, 119 citations in OpenAlex.
- Canonical and noncanonical autophagy in immunity.Immunity · 2026Review
- DNA damage in macrophages drives immune autoreactivity via nuclear antigen presentation.Nature aging · 2026Article
- Autophagy in Rheumatoid Arthritis: Molecular Mechanisms, Diagnostic Biomarkers, and Emerging Therapeutic Strategies.Inflammation · 2026Review
- A review of autophagy in the pancreas: normal physiology and pathophysiology.Autophagy reports · 2026Review
- Autophagy modulation in gynaecologic oncology: insights into immune regulation and therapeutic potential.Frontiers in immunology · 2026Review
- Regulatory T cells and peripheral immune tolerance: key mechanisms and therapeutic strategies for cardiovascular diseases.Frontiers in immunology · 2026Review
- Autophagy and mitophagy in dermatological disease: a comprehensive review from molecular pathways to therapeutic frontiers.Biology direct · 2025Review
- Unraveling the mechanisms of bone diseases: targeting dendritic cells in osteoimmunology for internal homeostasis balance.Bone research · 2025Review
- Role of autophagy in rejection after solid organ transplantation: A systematic review of the literature.World journal of transplantation · 2025Review
- Autophagy mediated immune response regulation and drug resistance in cancer.Molecular biology reports · 2025Review
- Autophagy in tumor immune escape and immunotherapy.Molecular cancer · 2025Review
- Epidermal maintenance of Langerhans cells relies on autophagy-regulated lipid metabolism.The Journal of cell biology · 2025Article
- Increased interferon I signaling, DNA damage response and evidence of T-cell exhaustion in a patient with combined interferonopathy (Aicardi-Goutières Syndrome, AGS) and cohesinopathy (Cornelia de Lange Syndrome, CdLS).Pediatric rheumatology online journal · 2025Article
- CD137-expressing regulatory T cells in cancer and autoimmune diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Autophagy in inflammatory bowel disease: immunization, etiology, and therapeutic potential.Frontiers in immunology · 2025Review
- The endoplasmic reticulum stress status of CD4+ T lymphocytes and its association with mTOR-mediated autophagic-lysosomal disorder in elderly sepsis patients.Frontiers in immunology · 2025Observational
- Review
- Regulatory T cells protect against diabetic cardiomyopathy in db/db mice.Journal of diabetes investigation · 2024Article
- CTLA-4 expression on CD4Frontiers in immunology · 2024Article
- Disulfidptosis-related signatures for prognostic and immunotherapy reactivity evaluation in hepatocellular carcinoma.European journal of medical research · 2023Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 8 institutions in 6 countries.
Funding
Abstract
Design of efficacious Treg-based therapies and establishment of clinical tolerance in autoimmune diseases have proven to be challenging. The clinical implementation of Treg immunotherapy has been hampered by various impediments related to the stability and isolation procedures of Tregs as well as the specific in vivo targets of Treg modalities. Herein, we have demonstrated that Foxp3+ Tregs potently suppress autoimmune responses in vivo through inhibition of the autophagic machinery in DCs in a cytotoxic T-lymphocyte-associated protein 4-dependent (CTLA4-dependent) manner. Autophagy-deficient DCs exhibited reduced immunogenic potential and failed to prime autoantigen-specific CD4+ T cells to mediate autoimmunity. Mechanistically, CTLA4 binding promoted activation of the PI3K/Akt/mTOR axis and FoxO1 nuclear exclusion in DCs, leading to decreased transcription of the autophagy component microtubule-associated protein 1 light chain 3β (Lc3b). Human DCs treated with CTLA4-Ig, a fusion protein composed of the Fc region of IgG1 and the extracellular domain of CTLA4 (also known as abatacept, marketed as Orencia), demonstrated reduced levels of autophagosome formation, while DCs from CTLA4-Ig-treated rheumatoid arthritis patients displayed diminished LC3B transcripts. Collectively, our data identify the canonical autophagy pathway in DCs as a molecular target of Foxp3+ Treg-mediated suppression that leads to amelioration of autoimmune responses. These findings may pave the way for the development of therapeutic protocols that exploit Tregs for the treatment of autoimmunity as well as diseases in which disturbed tolerance is a common denominator.
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Registered trials
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.