OSCR

Senescence-like cells recruit γδ T cells to drive prolonged hyposmia after SARS-CoV-2 infection in mice.

Overview

Authors: Shunya Tsuji1,2, Sosuke Nakano1, Koyu Ito1, Shohei Minami3, Ken Uemura1, Yusuke Konishi1, Masahiro Wakita1, Yumiko Okumura1, Shimpei Kawamoto1,4,5,6, Akari Matsuki7, Shinji Nakaoka7, Chikako Ono8,9, Hiroo Takahashi10, Itsuki Anzai11, Tokiko Watanabe9,11, Akiyoshi Uezumi12, Yoshiharu Matsuura8,9, Takeshi Kobayashi3,9, Toru Okamoto13, Akio Tsuboi14, Masataka Asagiri2, Eiji Hara1,9,15
ORCID iDs: Shunya Tsuji, Shimpei Kawamoto, Akari Matsuki, Chikako Ono, Itsuki Anzai, Toru Okamoto, Akio Tsuboi, Eiji Hara
15 affiliations
  1. Department of Molecular Biology, Research Institute for Microbial Diseases, The University of Osaka, Suita, Japan
  2. Department of Pharmacology, Yamaguchi University Graduate School of Medicine, Ube, Japan
  3. Department of Virology, Research Institute for Microbial Diseases, The University of Osaka, Suita, Japan
  4. HealthSpan Research Center, Tohoku University, Sendai, Japan
  5. Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan
  6. Organization for Advanced Studies, Tohoku University, Sendai, Japan
  7. Graduate School of Life Science, Hokkaido University, Sapporo, Japan
  8. Laboratory of Virus Control, Research Institute for Microbial Diseases, The University of Osaka, Suita, Japan
  9. Center for Infectious Disease Education and Research, The University of Osaka, Suita, Japan
  10. Department of Molecular Neurobiology, Graduate School of Medicine, Kagawa University, Kagawa, Japan
  11. Department of Molecular Virology, Research Institute for Microbial Diseases, The University of Osaka, Suita, Japan
  12. Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
  13. Juntendo University School of Medicine, Tokyo, Japan
  14. Graduate School of Pharmaceutical Sciences, The University of Osaka, Suita, Japan
  15. Immunology Frontier Research Center, The University of Osaka, Suita, Japan
Institutions: Yamaguchi University (Japan); The University of Osaka (Japan); Tohoku University (Japan); Hokkaido University (Japan); Kagawa University (Japan); Medical Institute of Bioregulation, Kyushu University (Japan); Juntendo University (Japan)
Journal: EMBO reports, volume 27, issue 10, pages 2526-2548
Dates: received 23 January 2026; accepted 26 March 2026; published online 10 April 2026; in print May 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s44319-026-00769-6 · PMID 41963730 · PMCID PMC13219478 · OpenAlex W7153056974
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: mouse (organism), other condition (population), cellular / molecular (subfield)
Methods: Statistics, Evoked potentials
Keywords: Immunology, Microbiology, Virology & Host Pathogen Interaction, Molecular Biology of Disease
MeSH: Anosmia*, COVID-19*, Intraepithelial Lymphocytes*, Receptors, Antigen, T-Cell, gamma-delta*, SARS-CoV-2*, Animals, Cellular Senescence, Chemokine CXCL9, Disease Models, Animal, Fibroblasts, Interferon-gamma, Interleukin-17, Mice, Mice, Inbred C57BL, Mice, Knockout, Olfactory Mucosa, Olfactory Receptor Neurons, T-Cell Senescence (* major topic)
Topic: Olfactory and Sensory Function Studies (Sensory Systems, Neuroscience), according to OpenAlex
Funding: MEXT | Japan Society for the Promotion of Science (JSPS) (JP25K00099, JP23K06481, JP25H00443); Japan Agency for Medical Research and Development (JP25gm1710004h0004, JP25zf0127008h0002); MEXT | Japan Science and Technology Agency (JST) (JPMJFR2308, JPMJMS2022); Mitsubishi Foundation (202012016); Ministry of Education, Culture, Sports, Science and Technology (JPMXP1323015484); OU Master Plan Implementation Project promoted under the University of Osaka; Takeda Science Foundation; Uehara Memorial Foundation; Lotte Foundation; Nagase Science and Technology Foundation
Citations: cited by 1 paper (Europe PMC); 48 references in the paper

Abstract

Persistent hyposmia is a hallmark of post COVID-19 conditions, yet the mechanisms sustaining olfactory dysfunction after viral clearance remain poorly understood. Here, using mouse models of SARS-CoV-2 infection, we show that virus-induced senescence-like changes in uninfected olfactory mucosal fibroblasts persist long after viral clearance and drive prolonged olfactory dysfunction. These senescence-like cells secrete SASP factors, including IFNγ, CXCL9, and CXCL11, thereby recruiting γδ T cells to the olfactory mucosa. The accumulated γδ T cells produce excessive IL-17A, which acts on IL-17 receptor A expressed on olfactory sensory neurons, leading to sustained impairment of their function. Genetic ablation of senescence pathways (p16/p21 double knockout), pharmacological elimination of senescent cells with the senolytic drug ABT263, or olfactory neuron-specific deletion of IL-17 receptor A each significantly alleviate prolonged olfactory dysfunction. These findings identify a senescence–γδ T cell–IL-17A axis as a key driver of prolonged hyposmia following SARS-CoV-2 infection in mice.

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.

Tracing map

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

Data

Data links

Data availability

No primary datasets have been generated and deposited for this study.

The source data of this paper are collected in the following database record: biostudies:S-SCDT-10_1038-S44319-026-00769-6 (https://www.ebi.ac.uk/biostudies/sourcedata/studies/S-SCDT-10_1038-S44319-026-00769-6).

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, 29 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 22 authors, 4 keywords, 18 MeSH terms, 10 funders, 48 references.

Cite

This paper

Tsuji, S., Nakano, S., Ito, K., Minami, S., Uemura, K., Konishi, Y., Wakita, M., Okumura, Y., Kawamoto, S., Matsuki, A., Nakaoka, S., Ono, C., Takahashi, H., Anzai, I., Watanabe, T., Uezumi, A., Matsuura, Y., Kobayashi, T., Okamoto, T., . . . Hara, E. (2026). Senescence-like cells recruit γδ T cells to drive prolonged hyposmia after SARS-CoV-2 infection in mice. EMBO reports, 27(10), 2526-2548. https://doi.org/10.1038/s44319-026-00769-6

BibTeX

@article{tsuji2026senescence,
author = {Tsuji, Shunya and Nakano, Sosuke and Ito, Koyu and Minami, Shohei and Uemura, Ken and Konishi, Yusuke and Wakita, Masahiro and Okumura, Yumiko and Kawamoto, Shimpei and Matsuki, Akari and Nakaoka, Shinji and Ono, Chikako and Takahashi, Hiroo and Anzai, Itsuki and Watanabe, Tokiko and Uezumi, Akiyoshi and Matsuura, Yoshiharu and Kobayashi, Takeshi and Okamoto, Toru and Tsuboi, Akio and Asagiri, Masataka and Hara, Eiji},
title = {{Senescence-like cells recruit γδ T cells to drive prolonged hyposmia after SARS-CoV-2 infection in mice}},
journal = {EMBO reports},
year = {2026},
month = apr,
volume = {27},
number = {10},
pages = {2526--2548},
publisher = {Nature Publishing Group},
issn = {1469-221X},
doi = {10.1038/s44319-026-00769-6},
url = {https://doi.org/10.1038/s44319-026-00769-6},
pmid = {41963730},
pmcid = {PMC13219478}
}

RIS

TY - JOUR
AU - Tsuji, Shunya
AU - Nakano, Sosuke
AU - Ito, Koyu
AU - Minami, Shohei
AU - Uemura, Ken
AU - Konishi, Yusuke
AU - Wakita, Masahiro
AU - Okumura, Yumiko
AU - Kawamoto, Shimpei
AU - Matsuki, Akari
AU - Nakaoka, Shinji
AU - Ono, Chikako
AU - Takahashi, Hiroo
AU - Anzai, Itsuki
AU - Watanabe, Tokiko
AU - Uezumi, Akiyoshi
AU - Matsuura, Yoshiharu
AU - Kobayashi, Takeshi
AU - Okamoto, Toru
AU - Tsuboi, Akio
AU - Asagiri, Masataka
AU - Hara, Eiji
TI - Senescence-like cells recruit γδ T cells to drive prolonged hyposmia after SARS-CoV-2 infection in mice
T2 - EMBO reports
J2 - EMBO Rep
PY - 2026
DA - 2026/04/10
VL - 27
IS - 10
SP - 2526
EP - 2548
SN - 1469-221X
PB - Nature Publishing Group
DO - 10.1038/s44319-026-00769-6
UR - https://doi.org/10.1038/s44319-026-00769-6
LA - en
ER -

CSL-JSON

{
"id": "10.1038/s44319-026-00769-6",
"type": "article-journal",
"title": "Senescence-like cells recruit γδ T cells to drive prolonged hyposmia after SARS-CoV-2 infection in mice",
"container-title": "EMBO reports",
"author": [
{
"family": "Tsuji",
"given": "Shunya"
},
{
"family": "Nakano",
"given": "Sosuke"
},
{
"family": "Ito",
"given": "Koyu"
},
{
"family": "Minami",
"given": "Shohei"
},
{
"family": "Uemura",
"given": "Ken"
},
{
"family": "Konishi",
"given": "Yusuke"
},
{
"family": "Wakita",
"given": "Masahiro"
},
{
"family": "Okumura",
"given": "Yumiko"
},
{
"family": "Kawamoto",
"given": "Shimpei"
},
{
"family": "Matsuki",
"given": "Akari"
},
{
"family": "Nakaoka",
"given": "Shinji"
},
{
"family": "Ono",
"given": "Chikako"
},
{
"family": "Takahashi",
"given": "Hiroo"
},
{
"family": "Anzai",
"given": "Itsuki"
},
{
"family": "Watanabe",
"given": "Tokiko"
},
{
"family": "Uezumi",
"given": "Akiyoshi"
},
{
"family": "Matsuura",
"given": "Yoshiharu"
},
{
"family": "Kobayashi",
"given": "Takeshi"
},
{
"family": "Okamoto",
"given": "Toru"
},
{
"family": "Tsuboi",
"given": "Akio"
},
{
"family": "Asagiri",
"given": "Masataka"
},
{
"family": "Hara",
"given": "Eiji"
}
],
"container-title-short": "EMBO Rep",
"volume": "27",
"issue": "10",
"page": "2526-2548",
"DOI": "10.1038/s44319-026-00769-6",
"PMID": "41963730",
"PMCID": "PMC13219478",
"ISSN": "1469-221X",
"publisher": "Nature Publishing Group",
"URL": "https://doi.org/10.1038/s44319-026-00769-6",
"language": "en",
"issued": {
"date-parts": [
[
2026,
4,
10
]
]
}
}

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.1038/s44321-026-00400-0
Tomatidine is a senotherapeutic compound that improves cognitive function and reduces cellular senescence in aged mice.
Journal: EMBO molecular medicine
In common: mouse, cellular / molecular, 2 references
[2] doi:10.1038/s41467-026-76232-w [code]
Th17 effector cytokines induce shared and distinct microglial and endothelial cell responses in a mouse model for post-streptococcal encephalitis.
Journal: Nature communications
In common: other condition, mouse, cellular / molecular, 1 reference
[3] doi:10.1038/s41467-026-76156-5 [code]
Longitudinal analysis reveals myeloid cell contributions to murine neuroPASC pathogenesis.
Journal: Nature communications
In common: other condition, mouse, cellular / molecular, 1 reference
[4] doi:10.1111/bpa.70129
Brain metastasis-associated fibroblasts shape the tumour microenvironment to enhance cancer cell invasion.
Journal: Brain pathology (Zurich, Switzerland)
In common: other condition, cellular / molecular, 1 reference
[5] doi:10.3389/fimmu.2026.1776555 [code]
Multi-omics analysis of long COVID (post-COVID-19 condition) reveals persistent mitochondrial dysfunction, suppressed oxidative phosphorylation, and immune dysregulation.
Journal: Frontiers in immunology
In common: other condition, cellular / molecular, 1 reference
[6] doi:10.1016/j.isci.2026.115821
Virus-host interactome reveals host cellular pathways perturbed by tick-borne encephalitis virus infection.
Journal: iScience
In common: other condition, cellular / molecular, 1 reference
[7] doi:10.1038/s41467-026-72639-7
Neuregulin-1 facilitates myelin regeneration through microglia-mediated mechanisms in a mouse model of chronic demyelination.
Journal: Nature communications
In common: mouse, cellular / molecular, 1 reference
[8] doi:10.1186/s12974-026-03794-3
Single-cell omics and flow cytometry identify distinct immune states of dural and brain-infiltrating IL-17-producing γδ T cells after experimental stroke.
Journal: Journal of neuroinflammation
In common: mouse, cellular / molecular, 1 reference
[9] doi:10.1016/j.bbih.2026.101274 [code]
Brain dynamics of attentional, default-mode and limbic networks are disrupted at rest in post-COVID-19 syndrome.
Journal: Brain, behavior, & immunity - health
In common: other condition, 1 reference
[10] doi:10.1038/s41598-026-51082-0
Non-uniform endogenous regeneration of olfactory sensory neuron axons across the mouse olfactory bulb.
Journal: Scientific reports
In common: mouse, 1 reference

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Sign in with ORCID to claim this paper as one of its authors, correct its record or validate its tracing map: when the paper's metadata lists your ORCID iD, you are recognized at once. Maintainers of its code: sign in with GitHub, then claim the repository on your account page.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion, reproductions, activity

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.