KLF2 controls thymic epithelial cell homeostasis, impacting regulatory T cell development and immune tolerance.
Overview
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal
Abstract
T cell development depends on specialized thymic microenvironments formed by cortical (c) and medullary (m) thymic epithelial cells (TECs), which arise from a common epithelial progenitor. However, the molecular mechanisms that govern TEC differentiation and function remain poorly understood. Particularly, mTECs display remarkable functional heterogeneity driven by complex genetic programs essential for central tolerance. Here, we investigated the role of the transcription factor KLF2 in TEC biology. TEC-specific deletion of KLF2 (KLF2 cKO) in mice impairs mTEC maintenance and selectively remodels transcriptional programs across cTEC and mTEC subsets, including several recently identified mimetic TECs. These perturbations imprint sustained thymic dysfunction and restrict regulatory T cell differentiation and function. Furthermore, KLF2 cKO mice show increased lymphocytic infiltration in peripheral tissues in aged and autoimmune-prone models, suggesting an increased susceptibility to the breakdown of immunological self-tolerance. Our findings highlight KLF2 as a critical regulator of TEC homeostasis and the prevention of autoimmunity.
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Code
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ebi.ac.uk/ena
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Data
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Version 1, 30 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 5 authors, 1 keyword, 6 funders, 49 references, 27 RRIDs.
Cite
This paper
Ferreirinha, P., Rodrigues, P. M., Sobral, F., Cavadas, B., & Alves, N. L. (2026). KLF2 controls thymic epithelial cell homeostasis, impacting regulatory T cell development and immune tolerance. iScience, 29(4), 115161. https://
BibTeX
@article{ferreirinha2026
author = {Ferreirinha, Pedro and Rodrigues, Pedro M. and Sobral, Francisco and Cavadas, Bruno and Alves, Nuno L.},
title = {{KLF2 controls thymic epithelial cell homeostasis, impacting regulatory T cell development and immune tolerance}},
journal = {iScience},
year = {2026},
month = mar,
volume = {29},
number = {4},
pages = {115161},
publisher = {Elsevier},
issn = {2589-0042},
doi = {10.1016/
url = {https://
pmid = {41884002},
pmcid = {PMC13010103}
}
RIS
TY - JOUR
AU - Ferreirinha, Pedro
AU - Rodrigues, Pedro M.
AU - Sobral, Francisco
AU - Cavadas, Bruno
AU - Alves, Nuno L.
TI - KLF2 controls thymic epithelial cell homeostasis, impacting regulatory T cell development and immune tolerance
T2 - iScience
J2 - iScience
PY - 2026
DA - 2026/
VL - 29
IS - 4
SP - 115161
SN - 2589-0042
PB - Elsevier
DO - 10.1016/
UR - https://
LA - en
ER -
CSL-JSON
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