ArticleThe Journal of experimental medicine2016
Intestinal microbiota sustains inflammation and autoimmunity induced by hypomorphic RAG defects.
Article in The Journal of experimental medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 69 citations in OpenAlex.
- RAG1 lentiviral gene therapy restores T-cell development of RAG1-SCID patient cells in artificial thymic organoids.Blood advances · 2025Trial
- Cerebral ischaemic stroke results in altered mucosal antibody responses and host-commensal microbiota interactions.Brain, behavior, and immunity · 2026Article
- Immunopathological and microbial signatures of inflammatory bowel disease in partial RAG deficiency.The Journal of experimental medicine · 2025Article
- Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.Science immunology · 2025Article
- A partial human LCK defect causes a T cell immunodeficiency with intestinal inflammation.The Journal of experimental medicine · 2024Article
- Autoimmunity in Primary Immunodeficiencies (PID).Clinical reviews in allergy & immunology · 2023Review
- Dysbiosis and primary B-cell immunodeficiencies: current knowledge and future perspective.Immunologic research · 2023Review
- Excision of mesenteric lymph nodes alters gut microbiota and impairs social dominance in adult mice.Brain and behavior · 2023Article
- Monogenic inflammatory bowel disease-genetic variants, functional mechanisms and personalised medicine in clinical practice.Human genetics · 2023Review
- Partial RAG deficiency in humans induces dysregulated peripheral lymphocyte development and humoral tolerance defect with accumulation of T-betNature immunology · 2022Article
- Treg-associated monogenic autoimmune disorders and gut microbial dysbiosis.Pediatric research · 2022Review
- Understanding inborn errors of immunity: A lens into the pathophysiology of monogenic inflammatory bowel disease.Frontiers in immunology · 2022Review
- Immunoglobulin A, an Active Liaison for Host-Microbiota Homeostasis.Microorganisms · 2021Review
- Intestinal immunoregulation: lessons from human mendelian diseases.Mucosal immunology · 2021Review
- Vertically transferred maternal immune cells promote neonatal immunity against early life infections.Nature communications · 2021Article
- RAG deficiencies: Recent advances in disease pathogenesis and novel therapeutic approaches.European journal of immunology · 2021Review
- The Influence of Diet on Oxidative Stress and Inflammation Induced by Bacterial Biofilms in the Human Oral Cavity.Materials (Basel, Switzerland) · 2021Review
- Review
- Gut Microbiota-Host Interactions in Inborn Errors of Immunity.International journal of molecular sciences · 2021Review
- The Roles of CCR9/CCL25 in Inflammation and Inflammation-Associated Diseases.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
20 authors at 11 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Omenn syndrome (OS) is caused by hypomorphic Rag mutations and characterized by a profound immunodeficiency associated with autoimmune-like manifestations. Both in humans and mice, OS is mediated by oligoclonal activated T and B cells. The role of microbial signals in disease pathogenesis is debated. Here, we show that Rag2(R229Q) knock-in mice developed an inflammatory bowel disease affecting both the small bowel and colon. Lymphocytes were sufficient for disease induction, as intestinal CD4 T cells with a Th1/Th17 phenotype reproduced the pathological picture when transplanted into immunocompromised hosts. Moreover, oral tolerance was impaired in Rag2(R229Q) mice, and transfer of wild-type (WT) regulatory T cells ameliorated bowel inflammation. Mucosal immunoglobulin A (IgA) deficiency in the gut resulted in enhanced absorption of microbial products and altered composition of commensal communities. The Rag2(R229Q) microbiota further contributed to the immunopathology because its transplant into WT recipients promoted Th1/Th17 immune response. Consistently, long-term dosing of broad-spectrum antibiotics (ABXs) in Rag2(R229Q) mice ameliorated intestinal and systemic autoimmunity by diminishing the frequency of mucosal and circulating gut-tropic CCR9(+) Th1 and Th17 T cells. Remarkably, serum hyper-IgE, a hallmark of the disease, was also normalized by ABX treatment. These results indicate that intestinal microbes may play a critical role in the distinctive immune dysregulation of OS.
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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.