Evidence map›Paper›PMID 40994352›Full record

ArticleHaematologica2026

MHC disparity hampers thymus-dependent T-cell recovery post-hematopoietic transplantation through dysregulation of TGF-β1 and LRP6 pathways.

Ning Wu, Wei Ding, Jiashuo Wu, Min Ling, Keli Yue, Cong Cheng, Mingzhu Jia, Jiangying Liu, Xiao-Jun Huang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Haematologica, 2026. 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.

Ning WuPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing.
Wei DingPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing.
Jiashuo WuPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing.
Min LingPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing.
Keli YuePeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing.
Cong ChengPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing.
Mingzhu JiaPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing.
Jiangying LiuPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing. xys_liujiangying@pkuph.edu.cn.
Xiao-Jun HuangPeking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing. huangxiaojun@bjmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Clinical studies have demonstrated that recipients of allogeneic hematopoietic cell transplantation (alloHCT), particularly those undergoing HLA-haploidentical alloHCT (haploHCT), exhibit significant immune deficiencies. However, the extent to which major histocompatibility complex (MHC) disparity independently contributes to the observed lymphocyte deficiency post-alloHCT remains unclear. While MHC matching is crucial for thymic selection of T lymphocytes, it has yet to be reported whether haploHCT alters recipient thymus homeostasis compared to MHC-matched HCT and which signaling pathways are implicated in this alteration. In this study, we established mouse models of MHC-matched HCT and haploHCT without any transplant-associated complications. Our findings indicated that MHC disparity significantly disrupted thymic architecture, suppressed thymus-specific gene expression, and resulted in impaired T-cell recovery and functionality following transplantation. Single-cell transcriptomic analysis revealed abnormally enhanced interactions involving TGFB1-TGFBR3 and LRP6-CKLF between thymic lymphocytes and epithelial cells in haploHCT recipients. Furthermore, agonists targeting the TGF-β1 and LRP6 pathways were found to compromise the functional characteristics of normal thymic T cells; conversely, appropriate inhibition of these pathways restored the differentiation and maturation phenotypes of thymic T cells derived from haploHCT recipients. Our study elucidates the independent role of MHC disparity in regulating thymus homeostasis and T-cell recovery while identifying the functional involvement of the TGF-β1 and LRP6 pathways in this context. These findings provide novel insights into the mechanisms underlying immune recovery as well as potential therapeutic strategies for modulating thymic functions following haploHCT.

Indexed as

Hematopoietic Stem Cell TransplantationMajor Histocompatibility ComplexSignal TransductionThymus GlandT-LymphocytesTransforming Growth Factor beta1AnimalsHumansMiceTransplantation, HomologousTransforming Growth Factor beta1

Identifiers

PMID40994352
PMCPMC12951156

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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.