Evidence map›Paper›PMID 38142533›Full record

ArticleJournal of autoimmunity2024

Silencing of aryl hydrocarbon receptor repressor restrains Th17 cell immunity in autoimmune hepatitis.

Li Gao, Wei Zhang, Lina Zhang, Barbora Gromova, Guanqing Chen, Eva Csizmadia, Cortney Cagle, Silvia Nastasio, Yun Ma, Alan Bonder and 4 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of autoimmunity, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.6field-weighted citation impact, top 9% 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

19 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
  2. Article
  3. Experimental Models of Autoimmune Hepatitis: Disease Fidelity and Translational Relevance.Liver international : official journal of the International Association for the Study of the Liver · 2026
    Review
  4. Article
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  6. Review
  7. Review
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  12. Neutrophil-T cell cross talk in noninfectious liver diseases.American journal of physiology. Gastrointestinal and liver physiology · 2026
    Review
  13. Article
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  17. Review
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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

14 authors at 4 institutions in 4 countries.

Li GaoDepartment of Anesthesia, Critical Care & Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Endocrinology and Metabolism, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China. Electronic address: ligao001@hotmail.com.
Wei ZhangDepartment of Anesthesia, Critical Care & Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Endocrinology and Metabolism, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China. Electronic address: doctorzhangwei001@163.com.
Lina ZhangDepartment of Anesthesia, Critical Care & Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; School of Arts and Sciences, Tufts University, Medford, MA, USA. Electronic address: Linazhang2008@gmail.com.
Barbora GromovaDepartment of Anesthesia, Critical Care & Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia. Electronic address: b.gromova@gmail.com.
Guanqing ChenDepartment of Anesthesia, Critical Care & Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: gchen7@bidmc.harvard.edu.
Eva CsizmadiaDepartment of Anesthesia, Critical Care & Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: ecsizmad@bidmc.harvard.edu.
Cortney CagleDepartment of Anesthesia, Critical Care & Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: ccagle@bidmc.harvard.edu.
Silvia NastasioDepartment of Anesthesia, Critical Care & Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA, USA. Electronic address: Silvia.Nastasio@childrens.harvard.edu.
Yun MaInstitute of Liver Studies, School of Immunology & Microbial Sciences, Faculty of Life Sciences & Medicine, King's College London, London, UK. Electronic address: yun.ma@kcl.ac.uk.
Alan BonderDivision of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: abonder@bidmc.harvard.edu.
Vilas PatwardhanDivision of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: vpatward@bidmc.harvard.edu.
Simon C RobsonDepartment of Anesthesia, Critical Care & Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: srobson@bidmc.harvard.edu.
Sizun JiangCenter for Virology and Vaccine Research, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: sjiang3@bidmc.harvard.edu.
Maria Serena LonghiDepartment of Anesthesia, Critical Care & Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: mlonghi@bidmc.harvard.edu.
Beth Israel Deaconess Medical Center · USBoston Children's Hospital · USKing's College London · GBTufts University · US

Funding

Immunomodulatory effects of bilirubin are mediated through aryl hydrocarbon receptor, O2 and purinergic pathwaysR01DK108894 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI LONGHI, MARIA SERENA · 2017 to 2021
$2.0M
Alterations of aryl hydrocarbon receptor signaling in autoimmune hepatitisR01DK124408 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI LONGHI, MARIA SERENA · 2020 to 2022
$1.2M
PGC-1α, Purines and the Postmenopausal HeartR21AG065923 · NIA · BETH ISRAEL DEACONESS MEDICAL CENTER · PI MATYAL, ROBINA, ROBSON, SIMON C. · 2021 to 2022
$481k
NIA NIH HHS R21 AG065923NIDDK NIH HHS R01 DK108894NIDDK NIH HHS R01 DK124408
6 · The paper itself

Abstract

Th17-cells play a key role in the pathogenesis of autoimmune hepatitis (AIH). Dysregulation of Th17-cells in AIH is linked to defective response to aryl-hydrocarbon-receptor (AhR) activation. AhR modulates adaptive immunity and is regulated by aryl-hydrocarbon-receptor-repressor (AHRR), which inhibits AhR transcriptional activity. In this study, we investigated whether defective Th17-cell response to AhR derives from aberrant AHRR regulation in AIH. Th17-cells, obtained from the peripheral blood of AIH patients (n = 30) and healthy controls (n = 30) were exposed to AhR endogenous ligands, and their response assessed in the absence or presence of AHRR silencing. Therapeutic effects of AHRR blockade were tested in a model of Concanavalin-A (Con-A)-induced liver injury in humanized mice. AHRR was markedly upregulated in AIH Th17-cells, following exposure to l-kynurenine, an AhR endogenous ligand. In patients, silencing of AHRR boosted Th17-cell response to l-kynurenine, as reflected by increased levels of CYP1A1, the main gene controlled by AhR; and decreased IL17A expression. Blockade of AHRR limited the differentiation of naïve CD4-cells into Th17 lymphocytes; and modulated Th17-cell metabolic profile by increasing the levels of uridine via ATP depletion or pyrimidine salvage. Treatment with 2'-deoxy-2'-fluoro-d-arabinonucleic acid (FANA) oligonucleotides to silence human AHRR in vivo, reduced ALT levels, attenuated lymphocyte infiltration on histology, and heightened frequencies of regulatory immune subsets in NOD/scid/gamma mice, reconstituted with human CD4 cells, and exposed to Con-A. In conclusion, blockade of AHRR in AIH restores Th17-cell response to AHR, and limits Th17-cell differentiation through generation of uridine. In vivo, silencing of AHRR attenuates liver damage in NOD/scid/gamma mice. Blockade of AHRR might therefore represent a novel therapeutic strategy to modulate effector Th17-cell immunity and restore homeostasis in AIH.

Indexed as

Hepatitis, AutoimmuneReceptors, Aryl HydrocarbonAnimalsBasic Helix-Loop-Helix ProteinsHumansHydrocarbonsKynurenineMiceMice, Inbred NODRepressor ProteinsTh17 CellsUridineAHR protein, humanAhr protein, mouseBasic Helix-Loop-Helix ProteinsHydrocarbonsKynurenineReceptors, Aryl HydrocarbonRepressor ProteinsUridineAHRAHRRAIHTh17 cells

Identifiers

PMID38142533
PMCPMC10981568
OpenAlexW4390151054

What OpenQuestion holds

Textmetadata
LicenceTDM
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.