ArticleJCI insight2021
Failure of thymic deletion and instability of autoreactive Tregs drive autoimmunity in immune-privileged liver.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
8 citing papers in PubMed, 20 citations in OpenAlex.
- H19 and the PD-1/PD-L1 Axis in hepatocellular carcinoma and colorectal cancer: emerging evidence, mechanistic links, and therapeutic perspectives.Clinical and experimental medicine · 2026Review
- IL-15 Plus Thymosin α1 Reduces Senescent Hepatic CD8Journal of gastroenterology and hepatology · 2026Article
- Regulatory T-cells in autoimmune hepatitis: An historical perspective with hints to the future.JHEP reports : innovation in hepatology · 2026Article
- Gut microbiota-derived metabolites modulate Treg/Th17 balance: novel therapeutic targets in autoimmune diseases.Frontiers in immunology · 2025Review
- Similar usage of T-cell receptor β-chain between tumor and adjacent normal tissue in hepatocellular carcinoma.Cancer medicine · 2024Article
- Tet2 deficiency drives liver microbiome dysbiosis triggering Tc1 cell autoimmune hepatitis.Cell host & microbe · 2022Article
- Animal Models for Autoimmune Hepatitis: Are Current Models Good Enough?Frontiers in immunology · 2022Review
- Dysfunctional Immune Regulation in Autoimmune Hepatitis: From Pathogenesis to Novel Therapies.Frontiers in immunology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The liver is an immune-privileged organ that can deactivate autoreactive T cells. Yet in autoimmune hepatitis (AIH), autoreactive T cells can defy hepatic control and attack the liver. To elucidate how tolerance to self-antigens is lost during AIH pathogenesis, we generated a spontaneous mouse model of AIH, based on recognition of an MHC class II-restricted model peptide in hepatocytes by autoreactive CD4+ T cells. We found that the hepatic peptide was not expressed in the thymus, leading to deficient thymic deletion and resulting in peripheral abundance of autoreactive CD4+ T cells. In the liver, autoreactive CD4+ effector T cells accumulated within portal ectopic lymphoid structures and maturated toward pathogenic IFN-γ and TNF coproducing cells. Expansion and pathogenic maturation of autoreactive effector T cells was enabled by a selective increase of plasticity and instability of autoantigen-specific Tregs but not of nonspecific Tregs. Indeed, antigen-specific Tregs were reduced in frequency and manifested increased IL-17 production, reduced epigenetic demethylation, and reduced expression of Foxp3. As a consequence, autoantigen-specific Tregs had a reduced suppressive capacity, as compared with that of nonspecific Tregs. In conclusion, loss of tolerance and the pathogenesis of AIH were enabled by combined failure of thymic deletion and peripheral regulation.
Indexed as
Identifiers
What OpenQuestion holds
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.