Evidence map›Paper›PMID 27139489›Full record

ArticleThe Journal of experimental medicine2016

Interferon-γ facilitates hepatic antiviral T cell retention for the maintenance of liver-induced systemic tolerance.

Zhutian Zeng, Lu Li, Yongyan Chen, Haiming Wei, Rui Sun, Zhigang Tian

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

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 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.9field-weighted citation impact, top 10% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Role of cellular senescence in hepatic diseases (Review).International journal of molecular medicine · 2025
    Review
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Review
  10. Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Liver-Mediated Adaptive Immune Tolerance.Frontiers in immunology · 2019
    Review
  18. Mechanisms of Hepatitis B Virus Persistence.Trends in microbiology · 2018
    Review
  19. Article
  20. HBV in 2016: Global and immunotherapeutic insights into hepatitis B.Nature reviews. Gastroenterology & hepatology · 2017
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Zhutian ZengInstitute of Immunology and the Key Laboratory of Innate Immunity and Chronic Disease, Chinese Academy of Science, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei 230027, China.
Lu LiInstitute of Immunology and the Key Laboratory of Innate Immunity and Chronic Disease, Chinese Academy of Science, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei 230027, China Hefei National Laboratory for Physical Sciences at the Microscale, Hefei 230027, China.
Yongyan ChenInstitute of Immunology and the Key Laboratory of Innate Immunity and Chronic Disease, Chinese Academy of Science, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei 230027, China.
Haiming WeiInstitute of Immunology and the Key Laboratory of Innate Immunity and Chronic Disease, Chinese Academy of Science, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei 230027, China.
Rui SunInstitute of Immunology and the Key Laboratory of Innate Immunity and Chronic Disease, Chinese Academy of Science, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei 230027, China.
Zhigang TianInstitute of Immunology and the Key Laboratory of Innate Immunity and Chronic Disease, Chinese Academy of Science, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei 230027, China Hefei National Laboratory for Physical Sciences at the Microscale, Hefei 230027, China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China tzg@ustc.edu.cn.
University of Science and Technology of China · CNHefei National Center for Physical Sciences at Nanoscale · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Persistent exposure to liver pathogens leads to systemic antigen-specific tolerance, a major cause of chronicity during hepatotropic infection. The mechanism regarding how this systemic tolerance is maintained remains poorly elucidated. In a well established mouse model of hepatitis B virus (HBV) persistence-induced systemic tolerance, we observed that interferon-γ (IFN-γ) deficiency led to complete loss of tolerance, resulting in robust anti-HBV responses upon peripheral vaccination. The recovery of vaccine-induced anti-HBV responses was mainly caused by the retained antigen-specific CD4(+) T cells rather than decreased functional inhibitory cells in the periphery. Mechanistically, HBV persistence induced sustained hepatic CD4(+) T cell-derived IFN-γ production. IFN-γ was found to promote CXCL9 secretion from liver-resident macrophages. This T cell chemokine facilitated the retention of antiviral CD4(+) T cells in the liver in a CXCR3-dependent manner. Hepatic sequestrated antiviral CD4(+) T cells subsequently underwent local apoptotic elimination partially via cytotoxic T lymphocyte-associated protein 4 ligation. These findings reveal an unexpected tolerogenic role for IFN-γ during viral persistence in the liver, providing new mechanistic insights regarding the maintenance of systemic antigen-specific tolerance during HBV persistence.

Indexed as

Immune ToleranceAnimalsCD4-Positive T-LymphocytesChemokine CXCL9Disease Models, AnimalHepatitis BHepatitis B virusInterferon-gammaLiverMaleMiceMice, KnockoutChemokine CXCL9Cxcl9 protein, mouseIFNG protein, mouseInterferon-gamma

Identifiers

PMID27139489
PMCPMC4886358
OpenAlexW2346641907

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

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.