Evidence map›Paper›PMID 41551409›Full record

ArticleJHEP reports : innovation in hepatology2026

Inhibition of estrogen receptor alpha stabilizes regulatory T cell function in autoimmune hepatitis.

Lina Zhang, Barbora Gromova, Du Hanh Nguyen, Cortney Cagle, Graziela S Gomes, William Li, Li Gao, Wei Zhang, Jonathon J Graham, Na Wang and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JHEP reports : innovation in hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Article
  2. 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
  3. Review
  4. 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

19 authors.

Lina ZhangDepartment of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Barbora GromovaDepartment of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Du Hanh NguyenDepartment of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Cortney CagleDepartment of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Graziela S GomesDepartment of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
William LiDepartment of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Li GaoDepartment of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Wei ZhangDepartment of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Jonathon J GrahamDepartment of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Na WangDepartment of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Ahmadreza KalbasiDepartment of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Eva CsizmadiaDepartment of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Angelina WeiDepartment of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Jessica CassavaughDepartment of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Alan BonderDivision of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Vilas PatwardhanDivision of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Sizun JiangCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Satya K KotaHarvard School of Dental Medicine, Department of Oral Medicine, Infection and Immunity, Boston, MA, USA.
Maria Serena LonghiDepartment of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background & Aims: Regulatory T cell (Treg) dysfunction is a hallmark of autoimmune hepatitis (AIH), a serious hepatopathy often progressing to end-stage liver disease despite immunosuppression. Treg impairment in AIH has been linked to defective signaling through the aryl hydrocarbon receptor (AhR), a modulator of adaptive immunity. Herein, we investigated whether increased estrogen receptor alpha (ERα), an AhR non-canonical binding partner, impacts Treg immunity and contributes to the sex bias observed in AIH. Methods: Tregs were isolated from the peripheral blood of pre-menopausal, post-menopausal and male patients with AIH, as well as controls. Their function, stability, transcriptome and response to AhR were assessed in the absence or presence of methylpiperidinopyrazole (MPP), an ERα-selective antagonist. Therapeutic effects of MPP were tested in a model of Concanavalin-A-induced liver injury in humanized mice. Results: ERα was upregulated in Tregs from pre-menopausal females with AIH (1.1 ± 0.3) compared with healthy pre-menopausal females (0.4 ± 0.1; Conclusions: ERα upregulation drives Treg dysfunction in pre-menopausal females with AIH and likely contributes to the sex bias in the disease. ERα blockade stabilizes Tregs and limits inflammation Impact and implications: Regulatory T cell (Treg) dysfunction plays a key role in the breakdown of immune tolerance in autoimmune hepatitis (AIH), a severe hepatopathy that often progresses to end-stage liver disease despite immunosuppression. Here we report that upregulation of estrogen receptor-alpha (ERα) alters Treg function and stability in pre-menopausal females with AIH, and that blockade of ERα using a specific antagonist stabilizes Tregs and curbs inflammation in humanized mice with liver injury. These findings implicate aberrant ERα signaling in the sex bias of AIH and support ERα inhibition as a potential therapeutic strategy to re-establish immune tolerance.

Indexed as

autoimmune hepatitisestrogen receptor-alphahypoxia-inducible factor 1-alpharegulatory T cells

Identifiers

PMID41551409
PMCPMC12804619

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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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.