ArticleProceedings of the National Academy of Sciences of the United States of America2012
Regulatory T cells that recognize a ubiquitous stress-inducible self-antigen are long-lived suppressors of autoimmune arthritis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 1 of them a synthesis that pooled it.
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.
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.
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Who cites it
70 citing papers in PubMed, 1 synthesis or guideline pooled it, 125 citations in OpenAlex.
- Autoimmune hepatitis in children: Guidelines of the Indian Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ISPGHAN).Hepatology international · 2025Guideline
- The Biologic IRL201805 Alters Immune Tolerance Leading to Prolonged Pharmacodynamics and Efficacy in Rheumatoid Arthritis Patients.International journal of molecular sciences · 2024Trial
- Identification ofFrontiers in immunology · 2026Article
- Human type 1 conventional dendritic cells contribute to skin transplant rejection.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025Article
- Antigen-specific immunotherapies for autoimmune disease.Nature reviews. Rheumatology · 2025Review
- Hspa13 Deficiency Impaired Marginal Zone B Cells Regulatory Function and Contributed to Lupus Pathogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Dual roles ofFrontiers in immunology · 2025Article
- Scavenger receptors: key players in the immunological puzzle of lupus.Frontiers in lupus · 2025Article
- Exploring the Interaction Mechanisms of Antibody-Mediated Immune Responses with Gout and Rheumatoid Arthritis Through a Bidirectional Two-Sample Mendelian Randomization Study.Journal of pain research · 2025Article
- Article
- Dual role of autoantibodies to heat shock proteins in autoimmune diseases.Frontiers in immunology · 2024Review
- Current status of immunological therapies for rheumatoid arthritis with a focus on antigen-specific therapeutic vaccines.Frontiers in immunology · 2024Review
- Vaccines for immune tolerance against autoimmune disease.Advanced drug delivery reviews · 2023Review
- Introducing Molecular Chaperones into the Causality and Prospective Management of Autoimmune Hepatitis.Digestive diseases and sciences · 2023Review
- Molecular Chaperone Receptors: An Update.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Heat shock proteins: Biological functions, pathological roles, and therapeutic opportunities.MedComm · 2022Review
- Heat Shock Protein 90 (Hsp90) and Hsp70 as Potential Therapeutic Targets in Autoimmune Skin Diseases.Biomolecules · 2022Review
- Pathological Relevance of Anti-Hsp70 IgG Autoantibodies in Epidermolysis Bullosa Acquisita.Frontiers in immunology · 2022Article
- Reestablish immune tolerance in rheumatoid arthritis.Frontiers in immunology · 2022Review
- Role of heat shock proteins in aging and chronic inflammatory diseases.GeroScience · 2021Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
Reestablishing self-tolerance in autoimmunity is thought to depend on self-reactive regulatory T cells (Tregs). Exploiting these antigen-specific regulators is hampered by the obscure nature of disease-relevant autoantigens. We have uncovered potent disease-suppressive Tregs recognizing Heat Shock Protein (Hsp) 70 self-antigens, enabling selective activity in inflamed tissues. Hsp70 is a major contributor to the MHC class II ligandome. Here we show that a conserved Hsp70 epitope (B29) is present in murine MHC class II and that upon transfer, B29-induced CD4(+)CD25(+)Foxp3(+) T cells suppress established proteoglycan-induced arthritis in mice. These self-antigen-specific Tregs were activated in vivo, and when using Lymphocyte Activation Gene-3 as a selection marker, as few as 4,000 cells sufficed. Furthermore, depletion of transferred Tregs abrogated disease suppression. Transferred cells exhibited a stable phenotype and were found in joints and draining lymph nodes up to 2 mo after transfer. Given that (i) B29 administration by itself suppressed disease, (ii) our findings were made with wild-type (T-cell receptor nontransgenic) Tregs, and (iii) the B29 human homolog is presented by HLA class II, we are nearing translation of antigen-specific Treg activation as a promising intervention for chronic inflammatory diseases.
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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.