ORIGINAL RESEARCH article
Front. Immunol.
Sec. T Cell Biology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1652359
CHASERR-CHD2 dynamics in T cell quiescence and its modulation by cyclosporine
Provisionally accepted
- 1Federal Center Research Fundamentals of Biotechnology (RAS), Moscow, Russia
- 2Moscow Center for Advanced Studies, Moscow, Russia
- 3HSE University, Moscow, Russia
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Background: CHASERR, a conserved long non-coding RNA located upstream of CHD2, transcriptionally represses CHD2 in cis. Both genes are highly expressed in lymphocytes, suggesting roles in immune regulation, though their functions remain undefined. Results: We identified elevated expression of CHASERR and CHD2 in na¨ıve and regulatory T cells through analysis of single-cell and bulk RNA-seq datasets. Both their promoters are bound by FOXP3, the key regulator of Treg cells, and FOXP1, the key regulator of na¨ıve T cell quiescence. Expression dynamics during early T cell activation revealed that a decline in CHASERR precedes a transient increase in CHD2. Correlation analysis linked CHASERR/CHD2 expression to quiescence-associated genes, suggesting a role in maintaining T cell homeostasis. We predicted and experimentally validated that cyclosporine A, a calcineurin inhibitor and potent immunosuppressant, mitigates the transcriptional changes induced by CHASERR loss, notably reducing elevated CHD2 expression in vitro after CHASERR knockdown. Conclusions: Our results position the CHASERR-CHD2 axis as a potential regulator of T cell homeostasis and activation. Furthermore, we propose cyclosporine A as a potential therapeutic strategy for conditions involving CHASERR deficiency.
Keywords: lncRNA, transcription, single-cell, T cell activation, T cell quiescence
Received: 23 Jun 2025; Accepted: 06 Oct 2025.
Copyright: © 2025 Budkina, Zubritsky, Marakulina and Medvedeva. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yulia A Medvedeva, jumedvedeva@gmail.com
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