ArticleNature communications2016
Gut environment-induced intraepithelial autoreactive CD4(+) T cells suppress central nervous system autoimmunity via LAG-3.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03766321 (Interplay Between Gut Microbiota and Adaptive Immunity in Amyotrophic Lateral Sclerosis), which is not on this map. Cited by 68 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Interplay Between Gut Microbiota and Adaptive Immunity in Amyotrophic Lateral Sclerosis: a Clinical Trial
Who cites it
68 citing papers in PubMed, 99 citations in OpenAlex.
- Parabacteroides goldsteinii mitigates parkinsonism in LRRK2 mutant mice by reducing neuroinflammation through Gut-Brain axis.Journal of advanced research · 2026Article
- LAG3 Gene Therapy Attenuates Autoimmune Uveitis by Regulating the PI3K/Akt Signaling Pathway.Investigative ophthalmology & visual science · 2026Article
- LAG-3Immunology · 2026Article
- The Microbiome-Neurodegeneration Interface: Mechanisms, Evidence, and Future Directions.Cells · 2026Review
- Gut microbiota and gut-derived metabolites in defining multiple sclerosis phenotypic continuum.Frontiers in immunology · 2026Review
- Intraepithelial Lymphocytes and LAIR1 Expression in Celiac Disease.Biomedicines · 2025Article
- Using the Key Characteristics Framework to Unlock the Mysteries of Aryl Hydrocarbon Receptor-Mediated Effects on the Immune System.Annual review of immunology · 2025Review
- CLEC16A in astrocytes promotes mitophagy and limits pathology in a multiple sclerosis mouse model.Nature neuroscience · 2025Article
- Single-cell analyses of intestinal epithelium reveal the dysregulation of gut immune microenvironment in systemic lupus erythematosus.Journal of translational medicine · 2025Article
- Co-expression of B7-H3 and LAG3 represents cytotoxicity of CD4Frontiers in immunology · 2025Article
- LAG-3-An incompletely understood target in cancer therapy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- A dynamic atlas of immunocyte migration from the gut.Science immunology · 2024Article
- Fecal Microbiota Transplantation in Amyotrophic Lateral Sclerosis: Clinical Protocol and Evaluation of Microbiota Immunity Axis.Methods in molecular biology (Clifton, N.J.) · 2024Article
- The Role of the Intestinal Microbiome in Multiple Sclerosis-Lessons to Be Learned from Hippocrates.Biology · 2023Review
- From bench to bedside: targeting lymphocyte activation gene 3 as a therapeutic strategy for autoimmune diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- Association betweenInternational journal of molecular sciences · 2022Article
- Metabolic regulation and function of T helper cells in neuroinflammation.Seminars in immunopathology · 2022Review
- LAG3 ectodomain structure reveals functional interfaces for ligand and antibody recognition.Nature immunology · 2022Article
- Fewer LAG-3Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- A Comprehensive Review on the Role of the Gut Microbiome in Human Neurological Disorders.Clinical microbiology reviews · 2022Review
8 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
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The gut environment has been found to significantly influence autoimmune diseases such as multiple sclerosis; however, immune cell mechanisms are unclear. Here we show that the gut epithelium of myelin oligodendrocyte glycoprotein(35-55)-specific T-cell receptor transgenic mice contains environmental stimuli-induced intraepithelial lymphocytes (IELs) that inhibit experimental autoimmune encephalomyelitis on transfer. These cells express surface markers phenotypical of 'induced' IELs, have a TH17-like profile and infiltrate the central nervous system (CNS). They constitutively express Ctla4 and Tgfb1 and markedly upregulate Lag3 expression in the CNS, thereby inhibiting inflammation. We also demonstrate the suppressive capability of CD4(+) IELs with alternative antigen specificities, their proliferation in response to gut-derived antigens and contribution of the microbiota and dietary aryl hydrocarbon receptor ligands to their induction. Thus, the gut environment favours the generation of autoreactive CD4(+) T cells with unique regulatory functions, potentially important for preventing CNS autoimmunity.
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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.