ArticleThe Journal of clinical investigation2012
MyD88 is critically involved in immune tolerance breakdown at environmental interfaces of Foxp3-deficient mice.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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.
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Who cites it
31 citing papers in PubMed, 54 citations in OpenAlex.
- Glutamine-dependent biosynthetic pathways fuel autoreactive T and B cells in Foxp3 deficiency-mediated disease.JCI insight · 2026Article
- Inborn errors of regulatory T-cell differentiation and function.The Journal of allergy and clinical immunology · 2025Review
- A New Probiotic Formulation Promotes Resolution of Inflammation in a Crohn's Disease Mouse Model by Inducing Apoptosis in Mucosal Innate Immune Cells.International journal of molecular sciences · 2024Article
- Intestinal factors promoting the development of RORγtFrontiers in immunology · 2023Review
- A Stk4-Foxp3-NF-κB p65 transcriptional complex promotes TScience immunology · 2022Article
- BANK1 interacts with TRAF6 and MyD88 in innate immune signaling in B cells.Cellular & molecular immunology · 2020Article
- T-Cell Deletion of MyD88 Connects IL17 and IκBζ to RAS Oncogenesis.Molecular cancer research : MCR · 2019Article
- Curcumin and Intestinal Inflammatory Diseases: Molecular Mechanisms of Protection.International journal of molecular sciences · 2019Review
- Microbiome Dependent Regulation of TFrontiers in immunology · 2019Review
- Host MyD88 signaling protects against acute graft-versus-host disease after allogeneic bone marrow transplantation.Clinical and experimental immunology · 2019Article
- Initiation of the inflammatory response after renal ischemia/reperfusion injury during renal transplantation.International urology and nephrology · 2018Review
- Toll-like Receptors and Inflammatory Bowel Disease.Frontiers in immunology · 2018Review
- DOCK8 Deficiency Presenting as an IPEX-Like Disorder.Journal of clinical immunology · 2017Article
- Irgm1 coordinately regulates autoimmunity and host defense at select mucosal surfaces.JCI insight · 2017Article
- Absence of functional fetal regulatory T cells in humans causes in utero organ-specific autoimmunity.The Journal of allergy and clinical immunology · 2017Article
- IL-4 production by group 2 innate lymphoid cells promotes food allergy by blocking regulatory T-cell function.The Journal of allergy and clinical immunology · 2016Article
- Intestinal microbiota sustains inflammation and autoimmunity induced by hypomorphic RAG defects.The Journal of experimental medicine · 2016Article
- The Microbiome, Systemic Immune Function, and Allotransplantation.Clinical microbiology reviews · 2016Review
- MyD88 Adaptor-Dependent Microbial Sensing by Regulatory T Cells Promotes Mucosal Tolerance and Enforces Commensalism.Immunity · 2015Article
- IL-33 signaling contributes to the pathogenesis of myeloproliferative neoplasms.The Journal of clinical investigation · 2015Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Tregs expressing the transcription factor Foxp3 suppress self-reactive T cells, prevent autoimmunity, and help contain immune responses to foreign antigens, thereby limiting the potential for inadvertent tissue damage. Mutations in the FOXP3 gene result in Treg deficiency in mice and humans, which leads to the development of a multisystem autoimmune inflammatory disease. The contribution of dysregulated innate immune responses to the pathogenesis of Foxp3 deficiency disease is unknown. In this study, we examined the role of microbial signals in the pathogenesis of Foxp3 deficiency disease by studying Foxp3 mutant mice that had concurrent deficiencies in TLR signaling pathways. Global deficiency of the common TLR adaptor MyD88 offered partial protection from Foxp3 deficiency disease. Specifically, it protected from disease at the environmental interfaces of the skin, lungs, and gut. In contrast, systemic disease, in the form of unrestrained lymphoproliferation, continued unabated. The effect of MyD88 deficiency at environmental interfaces involved the disruption of chemokine gradients that recruit effector T cells and DCs, resulting in their entrapment in secondary lymphoid tissues. These results suggests that Tregs have a key role in maintaining tolerance at host-microbial interfaces by restraining tonic MyD88-dependent proinflammatory signals. Moreover, microbial factors may play a substantial role in the pathogenesis of human autoimmune disease resulting from Treg deficiency.
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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.