Evidence map›Paper›PMID 41134666›Full record

ArticleCell reports2025

Optimal CXCR5 expression during Tfh maturation involves the Bhlhe40-Pou2af1 axis.

Xiaoliang Zhu, Xi Chen, Yaqiang Cao, Chengyu Liu, Zoey J Kline, Gangqing Hu, Sundar Ganesan, Tibor Z Veres, Difeng Fang, Shuai Liu and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Multimodal analysis definesbioRxiv : the preprint server for biology · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Xiaoliang ZhuMolecular and Cellular Immunoregulation Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Xi ChenMolecular and Cellular Immunoregulation Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Yaqiang CaoLaboratory of Epigenome Biology, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Chengyu LiuTransgenic Core Facility, National Heart Lung and Blood Institute, Bethesda, MD 20892, USA.
Zoey J KlineMolecular and Cellular Immunoregulation Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Gangqing HuLaboratory of Epigenome Biology, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Sundar GanesanBiological Imaging Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Tibor Z VeresLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Difeng FangMolecular and Cellular Immunoregulation Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Shuai LiuLaboratory of Epigenome Biology, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Danping WeiMolecular and Cellular Immunoregulation Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Hirofumi ShibataCell Signaling and Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Dominic P GolecCell Signaling and Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Hyunwoo ChungMolecular and Cellular Immunoregulation Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Ronald N GermainLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Pamela L SchwartzbergCell Signaling and Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Keji ZhaoLaboratory of Epigenome Biology, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Jinfang ZhuMolecular and Cellular Immunoregulation Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: jfzhu@niaid.nih.gov.

Funding

Transcriptional Regulation of Immune Cell Development, Activation and FunctionsZIAAI001169 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI ZHU, JINFANG · 2012 to 2025
$21.8M
Genetic and Biochemical Approaches to Tyrosine Kinase and Lymphocyte SignalingZIAAI001240 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SCHWARTZBERG, PAMELA · 2019 to 2025
$18.8M
Functional Biology Of T CellsZIAAI000758 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI GERMAIN, RONALD N · 2009 to 2025
$15.4M
Epigenetic Regulation of T cell differentiationZIAHL006030 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI ZHAO, KEJI · 2009 to 2025
$15.3M
Intramural NIH HHS ZIA AI000758Intramural NIH HHS ZIA AI001169Intramural NIH HHS ZIA AI001240Intramural NIH HHS ZIA HL006030
6 · The paper itself

Abstract

The pair of transcription factors Bcl6-Blimp1 is well known for follicular T helper (Tfh) early cell fate determination; however, the mechanism(s) for late regulation of CXCR5 during Tfh migration into germinal centers (GCs) is still unclear. In this study, we uncovered another pair of transcription factors, Bhlhe40-Pou2af1, that regulate CXCR5 expression. Pou2af1 was specifically expressed in Tfh cells, whereas Bhlhe40 expression was found to be high in non-Tfh cells. Pou2af1 promoted Tfh formation and migration into a GC by upregulating CXCR5 but not Bcl6, while Bhlhe40 repressed this process by inhibiting Pou2af1 expression. RNA sequencing analysis of antigen-specific Tfh cells generated in vivo confirmed the role of Bhlhe40-Pou2af1 axis in regulating optimal CXCR5 expression. Thus, the regulation of CXCR5 expression and migration of Tfh cells into a GC involves a transcriptional regulatory circuit consisting of Bhlhe40 and Pou2af1, which does not affect the Bcl6-Blimp1 circuit that determines the Tfh cell fate.

Indexed as

Basic Helix-Loop-Helix ProteinsHomeodomain ProteinsReceptors, CXCR5T Follicular Helper CellsAnimalsCell DifferentiationCell MovementGerminal CenterMiceMice, Inbred C57BLProto-Oncogene Proteins c-bcl-6Trans-ActivatorsBasic Helix-Loop-Helix ProteinsBhlhe40 protein, mouseCXCR5 protein, mouseHomeodomain ProteinsPou2af1 protein, mouseProto-Oncogene Proteins c-bcl-6Receptors, CXCR5Trans-ActivatorsBhlhe40CP: ImmunologyCXCR5follicular T helpergerminal centerPou2af1

Identifiers

PMID41134666
PMCPMC12744931

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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.