Evidence map›Paper›PMID 40189495›Full record

ArticleBMC medicine2025

Double-negative T cells in combination with ursodeoxycholic acid ameliorates immune-mediated cholangitis in mice.

Chunpan Zhang, Guangyong Sun, Hua Jin, Yunxiong Wei, Shimeng Zheng, Xiyu Wang, Xinyan Zhao, Dong Zhang, Jidong Jia

Abstract read
In one paragraph

Article in BMC medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

9 authors.

Chunpan Zhang *Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
Guangyong Sun *Medical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, No. 8 South Gongti Road, Beijing, 100020, China.
Hua JinMedical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, No. 8 South Gongti Road, Beijing, 100020, China.
Yunxiong WeiMedical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, No. 8 South Gongti Road, Beijing, 100020, China.
Shimeng ZhengMedical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, No. 8 South Gongti Road, Beijing, 100020, China.
Xiyu WangMedical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, No. 8 South Gongti Road, Beijing, 100020, China.
Xinyan ZhaoLiver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
Dong ZhangMedical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, No. 8 South Gongti Road, Beijing, 100020, China. zhangd@ccmu.edu.cn.
Jidong JiaLiver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China. jia_jd@ccmu.edu.cn.

Funding

Beijing Municipal Administration of Hospitals' Ascent Plan DFL20220103National Natural Science Foundation of China 81770598National Natural Science Foundation of China 81970503National Natural Science Foundation of China 82270606Natural Science Foundation of Beijing Municipality 7244319R&D Program of Beijing Municipal Education Commission KZ202210025036Youth Beijing Scholar No. 035
6 · The paper itself

Abstract

backgroundPrimary biliary cholangitis (PBC) is a liver-specific autoimmune disease. Treatment of PBC with ursodeoxycholic acid (UDCA) is not sufficient to prevent disease progression. Our previous study revealed that the number of hepatic double-negative T cells (DNT), which are unique regulatory T cells, was reduced in PBC patients. However, whether replenishment of DNT can prevent the progression of PBC remains unclear.

methodsDnTGFβRII (Tg) mice and 2OA-BSA-immunized mice received DNT alone or in combination with oral UDCA. After 6-12 weeks of treatment, these mice were assessed for serological changes, liver pathological manifestations and intrahepatic immune responses.

resultsAdoptive transfer of DNT alone significantly decreased serum levels of alanine transaminase (ALT), aspartate transaminase (AST), antimitochondrial antibody M2 (AMA-M2) and immunoglobulin M (IgM) in both Tg and 2OA-BSA-immunized PBC mouse models. In addition, DNT exhibited a strong killing effect on liver T cells and strong inhibition of their proliferation, but did not significantly improve the histology of PBC liver. However, combination therapy with DNT and oral UDCA predominantly ameliorated liver inflammation and significantly inhibited hepatic T and B cells. In vitro further study revealed that UDCA up-regulated the proliferation of DNT, increased the expression of the functional molecule perforin, and reduced the expression of NKG2A and endothelial cell protein C receptor (EPCR) through the farnesoid X receptor (FXR)/JNK signaling pathway in both mice and human DNT.

conclusionsA single transfer of DNT ameliorated PBC in mice, while combination therapy of DNT with oral UDCA displayed a better efficacy, with stronger inhibition of hepatic T and B cells. This study highlights the potential application of DNT-based combination therapy for PBC, especially for UDCA non-responders.

Indexed as

CholangitisLiver Cirrhosis, BiliaryT-LymphocytesUrsodeoxycholic AcidAdoptive TransferAnimalsDisease Models, AnimalFemaleLiverMaleMiceMice, Inbred C57BLUrsodeoxycholic AcidDouble-negative T cellsFarnesoid X receptorPrimary biliary cholangitisUrsodeoxycholic acid

Identifiers

PMID40189495
PMCPMC11974204

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Registered trials

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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.