Inflammatory conditions shape phenotypic and functional characteristics of lung-resident memory T cells in mice

Schmidt A, Fuchs J, Dedden M, Kocher K, Schülein C, Hübner J, Vieira Antao AI, Irrgang P, Oltmanns F, Viherlehto V, Leicht N, Rieker R, Geppert CI, Appelt U, Zundler S, Schober K, Lapuente D, Tenbusch M (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 16

Article Number: 3612

Journal Issue: 1

DOI: 10.1038/s41467-025-58931-y

Abstract

Lung tissue-resident memory T cells (TRM) are critical for the local control of respiratory tract infections caused by influenza A viruses (IAV). Here we compare TRM populations induced by intranasal adenoviral vector vaccines encoding hemagglutinin and nucleoprotein (NP) with those induced by an H1N1 infection in BALB/c mice. While vaccine-induced TRM express high levels of CD103 and persist longer in the lung parenchyma, short-lived, H1N1-induced TRM have a transcriptome associated with higher cytotoxic potential and distinct transcriptional profile as shown by single-cell RNA sequencing. In both the vaccine and H1N1 groups, NP-specific CD8⁺ T cells expand during heterologous influenza virus infection and protect the mice from disease. Meanwhile, lung inflammation in response to an infection with unrelated respiratory syncytial virus do not influence the fate of pre-existing TRM. Our preclinical work thus confirms that inflammatory conditions in the tissue shape the phenotypic and functional characteristics of TRM to serve relevant informations for optimizing mucosal vaccines.

Authors with CRIS profile

Anna Schmidt Institute of Clinical and Molecular Virology Jana Fuchs Professur für Genbasierte Immunisierungsverfahren Mark Dedden Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Katharina Kocher Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene Christine Schülein Lehrstuhl für Biochemie und Molekulare Medizin Ana Isabel Vieira Antao Institute of Clinical and Molecular Virology Friederike Oltmanns Institute of Clinical and Molecular Virology Vera Viherlehto Institute of Clinical and Molecular Virology Ralf Rieker Institute of Pathology Carol-Immanuel Geppert Institute of Pathology Uwe Appelt Klinisch-Molekularbiologisches Forschungszentrum Sebastian Zundler Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Kilian Schober Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene Dennis Lapuente Institute of Clinical and Molecular Virology Matthias Tenbusch Professur für Genbasierte Immunisierungsverfahren

How to cite

APA:

Schmidt, A., Fuchs, J., Dedden, M., Kocher, K., Schülein, C., Hübner, J.,... Tenbusch, M. (2025). Inflammatory conditions shape phenotypic and functional characteristics of lung-resident memory T cells in mice. Nature Communications, 16(1). https://doi.org/10.1038/s41467-025-58931-y

MLA:

Schmidt, Anna, et al. "Inflammatory conditions shape phenotypic and functional characteristics of lung-resident memory T cells in mice." Nature Communications 16.1 (2025).

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