Previous Article in Journal
Parkinson’s Disease: Bridging Gaps, Building Biomarkers, and Reimagining Clinical Translation
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Cells
Volume 14
Issue 15
10.3390/cells14151162
cells-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

NR2F6 as a Disease Driver and Candidate Therapeutic Target in Experimental Cerebral Malaria

by
Victoria E. Stefan
1,2,
Victoria Klepsch
3,*,
Nikolaus Thuille
3,
Martina Steinlechner
3,†,
Sebastian Peer
4,
Kerstin Siegmund
3,
Peter Lackner
5,6,
Erich Schmutzhard
7,
Karin Albrecht-Schgör
3,† and
Gottfried Baier
3
1
Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University Salzburg, 5020 Salzburg, Austria
2
Department of Biosciences and Medical Biology, University of Salzburg, 5020 Salzburg, Austria
3
Institute for Cell Genetics, Medical University of Innsbruck, 6020 Innsbruck, Austria
4
Internal Medicine V (Hematology and Oncology), Medical University of Innsbruck, 6020 Innsbruck, Austria
5
Klinik Floridsdorf, Vienna Healthcare Group, Department of Neurology, 1010 Vienna, Austria
6
Karl-Landsteiner-Institute for Clinical Research in Acute Neurology, 1010 Vienna, Austria
7
Department of Neurology, Medical University of Innsbruck, 6020 Innsbruck, Austria
*
Author to whom correspondence should be addressed.
†
Former member of Institute for Cell Genetics, Medical University of Innsbruck, 6020 Innsbruck, Austria.
Cells 2025, 14(15), 1162; https://doi.org/10.3390/cells14151162
Submission received: 27 June 2025 / Revised: 18 July 2025 / Accepted: 25 July 2025 / Published: 28 July 2025
(This article belongs to the Section Cell Signaling)
Versions Notes

Abstract

Cerebral malaria (CM) is the severe progression of an infection with Plasmodium falciparum, causing detrimental damage to brain tissue and is the most frequent cause of Plasmodium falciparum mortality. The critical role of brain-infiltrating CD8+ T cells in the pathophysiology of CM having been revealed, our investigation focuses on the role of NR2F6, an established immune checkpoint, as a candidate driver of CM pathology. We employed an experimental mouse model of CM based on Plasmodium berghei ANKA (PbA) infection to compare the relative susceptibility of Nr2f6-knock-out and wild-type C57BL6/N mice. As a remarkable result, Nr2f6 deficiency confers a significant survival benefit. In terms of mechanism, we detected less severe endotheliopathy and, hence, less damage to the blood–brain barrier (BBB), accompanied by decreased sequestered parasites and less cytotoxic T-lymphocytes within the brain, manifesting in a better disease outcome. We present evidence that NR2F6 deficiency renders mice more resistant to experimental cerebral malaria (ECM), confirming a causal and non-redundant role for NR2F6 in the progression of ECM disease. Consequently, pharmacological inhibitors of the NR2F6 pathway could be of use to bolster BBB integrity and protect against CM.
Keywords: experimental cerebral malaria (ECM); compromised blood–brain barrier (BBB) integrity; CD8+ T cell brain infiltration; nuclear receptor subfamily 2; group F; member 6 (NR2F6); innovative pharmacological therapy solution for CM experimental cerebral malaria (ECM); compromised blood–brain barrier (BBB) integrity; CD8+ T cell brain infiltration; nuclear receptor subfamily 2; group F; member 6 (NR2F6); innovative pharmacological therapy solution for CM

Share and Cite

MDPI and ACS Style

Stefan, V.E.; Klepsch, V.; Thuille, N.; Steinlechner, M.; Peer, S.; Siegmund, K.; Lackner, P.; Schmutzhard, E.; Albrecht-Schgör, K.; Baier, G. NR2F6 as a Disease Driver and Candidate Therapeutic Target in Experimental Cerebral Malaria. Cells 2025, 14, 1162. https://doi.org/10.3390/cells14151162

AMA Style

Stefan VE, Klepsch V, Thuille N, Steinlechner M, Peer S, Siegmund K, Lackner P, Schmutzhard E, Albrecht-Schgör K, Baier G. NR2F6 as a Disease Driver and Candidate Therapeutic Target in Experimental Cerebral Malaria. Cells. 2025; 14(15):1162. https://doi.org/10.3390/cells14151162

Chicago/Turabian Style

Stefan, Victoria E., Victoria Klepsch, Nikolaus Thuille, Martina Steinlechner, Sebastian Peer, Kerstin Siegmund, Peter Lackner, Erich Schmutzhard, Karin Albrecht-Schgör, and Gottfried Baier. 2025. "NR2F6 as a Disease Driver and Candidate Therapeutic Target in Experimental Cerebral Malaria" Cells 14, no. 15: 1162. https://doi.org/10.3390/cells14151162

APA Style

Stefan, V. E., Klepsch, V., Thuille, N., Steinlechner, M., Peer, S., Siegmund, K., Lackner, P., Schmutzhard, E., Albrecht-Schgör, K., & Baier, G. (2025). NR2F6 as a Disease Driver and Candidate Therapeutic Target in Experimental Cerebral Malaria. Cells, 14(15), 1162. https://doi.org/10.3390/cells14151162

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop