OSCR

Misregulation of T-box transcription factors drives BNP-NPR1 signalling underlying chronic itch.

Overview

Authors: Xiaolong Dai1, Michael Kitching2, Wenke Cheng1, Rengang Luo2, Lianlian Li1, Renkai Zhu2, Chunxu Shan2, Weiwei Chen1,3, Timo Buhl4, Andrea Szegedi5,6, Jorg Buddenkotte7,8,9, Shouming Xu1, Jiafu Wang2, Jianghui Meng2
ORCID iDs: Michael Kitching, Weiwei Chen, Timo Buhl, Jiafu Wang, Jianghui Meng
  1. School of Life Sciences, Henan University,Kaifeng, Henan China
  2. School of Biotechnology, Faculty of Science and Health, Dublin City University, Glasnevin,Dublin, Ireland
  3. Immuno Biotech Co. Ltd, Zhengzhou, Henan China
  4. Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen,Göttingen, Germany
  5. Department of Dermatology, Centre of Excellence, Faculty of Medicine, University of Debrecen,Debrecen, Hungary
  6. HUN-REN-DE Allergology Research Group, Debrecen, Hungary
  7. Department of Dermatology and Venereology, Hamad Medical Corporation,Doha, Qatar
  8. Translational Research Institute, Academic Health System, Hamad Medical Corporation,Doha, Qatar
  9. Dermatology Institute, Academic Health System, Hamad Medical Corporation,Doha, Qatar
Institutions: Henan University (China); Dublin City University (Ireland); Universitätsmedizin Göttingen (Germany); University of Debrecen (Hungary); Hamad Medical Corporation (Qatar)
Journal: Nature communications, volume 17, issue 1, article 8754
Dates: received 4 August 2025; accepted 3 July 2026; published online 17 July 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41467-026-75726-x · PMID 42469239 · PMCID PMC13493844 · OpenAlex W7169532853
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: human (organism), mouse (organism), cellular / molecular (subfield)
Methods: Spectral & time-frequency, Statistics, Smoothing, state filtering, decompositions, Preprocessing, Single-unit activity, calcium imaging
Keywords: Pruritus, Skin diseases, Transcriptional regulatory elements
MeSH: Natriuretic Peptide, Brain*, Pruritus*, Receptors, Atrial Natriuretic Factor*, T-Box Domain Proteins*, Animals, Chronic Disease, Dermatitis, Atopic, Female, Humans, Interleukin-13, Interleukin-4, Keratinocytes, Male, Mice, Mice, Knockout, Promoter Regions, Genetic, Sensory Receptor Cells, Signal Transduction, Skin (* major topic)
Topic: Dermatology and Skin Diseases (Dermatology, Medicine), according to OpenAlex
Funding: Science Foundation Ireland (SFI) (23/FFP-A/11956)
Citations: cited by 1 paper (Europe PMC); 70 references in the paper

Abstract

Chronic itch poses a significant clinical burden, with activation of the brain natriuretic peptide (BNP) pathway as a hallmark, though its transcriptional control remains unclear. We identify T-box transcription factor 20 (TBX20) as upregulated in skin of atopic dermatitis patients, with increased expression in NPR1+ keratinocytes. ChIP peak calling, ChIP-qPCR and dual-luciferase assays show TBX20 activates the NPR1 promoter. In mice, keratinocyte-specific TBX20 knockout (TBX20fl/fl; K14-Cre) reduces scratching, IL-4 and Oncostatin M levels, basophil markers, and decreases cutaneous NPR1 expression. TBX20 is also expressed in a subset of NPR1+ sensory neurons, and neuron-specific deletion similarly alleviates itch, basophil infiltration, and barrier dysfunction. RNA-seq identifies lipocalin-2 as a downstream effector of the TBX20-NPR1 axis, and its deletion reduces itch. Conversely, AAV-mediated TBX20 rescue exacerbates symptoms. Neuregulin 1 suppresses TBX20, attenuates IL-13-driven NPR1 signalling, and reduces itch. These findings define a TBX20-NPR1 axis as a critical regulator of chronic itch and skin dysfunction.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Code availability

This study did not involve the development of custom code. Accordingly, no custom code was generated or deposited in a public repository. Code used for the identification of TBX20 consensus sequences in ChIP peak calling related to Fig. 3a is provided in the Source Data file. These analyses were performed using established, publicly available software and packages.

Reproduced under the paper's license (CC BY), from the paper cited above.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none, so it has no map.

Data

Datasets cited

Data availability

All data described in this study are included in the manuscript and the accompanying Supporting Information. All RNA-seq datasets associated with this article have been deposited in the Gene Expression Omnibus (GEO) under accession code GSE281758 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE281758). All relevant raw data from figures generated in this study have been provided in the Source Data file. Source Data are provided with this paper70.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 14 authors, 3 keywords, 19 MeSH terms, 1 funder, 70 references.

Cite

This paper

Dai, X., Kitching, M., Cheng, W., Luo, R., Li, L., Zhu, R., Shan, C., Chen, W., Buhl, T., Szegedi, A., Buddenkotte, J., Xu, S., Wang, J., & Meng, J. (2026). Misregulation of T-box transcription factors drives BNP-NPR1 signalling underlying chronic itch. Nature communications, 17(1), 8754. https://doi.org/10.1038/s41467-026-75726-x

BibTeX

@article{dai2026misregulation,
author = {Dai, Xiaolong and Kitching, Michael and Cheng, Wenke and Luo, Rengang and Li, Lianlian and Zhu, Renkai and Shan, Chunxu and Chen, Weiwei and Buhl, Timo and Szegedi, Andrea and Buddenkotte, Jorg and Xu, Shouming and Wang, Jiafu and Meng, Jianghui},
title = {{Misregulation of T-box transcription factors drives BNP-NPR1 signalling underlying chronic itch}},
journal = {Nature communications},
year = {2026},
month = jul,
volume = {17},
number = {1},
pages = {8754},
publisher = {Nature Publishing Group},
issn = {2041-1723},
doi = {10.1038/s41467-026-75726-x},
url = {https://doi.org/10.1038/s41467-026-75726-x},
pmid = {42469239},
pmcid = {PMC13493844}
}

RIS

TY - JOUR
AU - Dai, Xiaolong
AU - Kitching, Michael
AU - Cheng, Wenke
AU - Luo, Rengang
AU - Li, Lianlian
AU - Zhu, Renkai
AU - Shan, Chunxu
AU - Chen, Weiwei
AU - Buhl, Timo
AU - Szegedi, Andrea
AU - Buddenkotte, Jorg
AU - Xu, Shouming
AU - Wang, Jiafu
AU - Meng, Jianghui
TI - Misregulation of T-box transcription factors drives BNP-NPR1 signalling underlying chronic itch
T2 - Nature communications
J2 - Nat Commun
PY - 2026
DA - 2026/07/17
VL - 17
IS - 1
SP - 8754
SN - 2041-1723
PB - Nature Publishing Group
DO - 10.1038/s41467-026-75726-x
UR - https://doi.org/10.1038/s41467-026-75726-x
LA - en
ER -

CSL-JSON

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