ArticleMucosal immunology2022
Clonotypic analysis of protective influenza M2e-specific lung resident Th17 memory cells reveals extensive functional diversity.
Article in Mucosal immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 46 citations in OpenAlex.
- Nasal CD4+ tissue-resident memory T cells provide cross-protective immunity to influenza.The Journal of experimental medicine · 2026Article
- The role of T cells in influenza infection and vaccination.Virologica Sinica · 2026Review
- T cell-macrophage interactions in tuberculosis: What we've got here is failure to communicate.Journal of internal medicine · 2026Review
- T-cell immunity against influenza virus does not require Th1 or Th17 master regulator transcription factors.Mucosal immunology · 2025Article
- Research Progress of Universal Influenza Vaccine.Vaccines · 2025Review
- Advances in Single-Cell Sequencing for Infectious Diseases: Progress and Perspectives.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Airway-resident memory CD4 T cell activation accelerates antigen presentation and T cell priming in draining lymph nodes.JCI insight · 2024Article
- Virus-specific Th17 Cells Are Induced by Human Cytomegalovirus after Renal Transplantation.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Opportunities and challenges for T cell-based influenza vaccines.Nature reviews. Immunology · 2024Review
- Review
- Single cell RNA-sequencing delineates CD8Theranostics · 2024Article
- A novel "prime and pull" strategy mediated by the combination of two dendritic cell-targeting designs induced protective lung tissue-resident memory T cells against H1N1 influenza virus challenge.Journal of nanobiotechnology · 2023Article
- CD8Nature communications · 2023Article
- Humoral Response to the Acetalated Dextran M2e Vaccine is Enhanced by Antigen Surface Conjugation.Bioconjugate chemistry · 2023Article
- Homologous Sequential Immunization Using Salmonella Oral Administration Followed by an Intranasal Boost with Ferritin-Based Nanoparticles Enhanced the Humoral Immune Response against H1N1 Influenza Virus.Microbiology spectrum · 2023Article
- Leveraging Exosomes as the Next-Generation Bio-Shuttles: The Next Biggest Approach against Th17 Cell Catastrophe.International journal of molecular sciences · 2023Review
- Tissue-resident memory T cells trigger rapid exudation and local antibody accumulation.Mucosal immunology · 2023Article
- Erratum: Type 1 regulatory T cell-mediated tolerance in health and disease.Frontiers in immunology · 2022Article
- Type 1 regulatory T cell-mediated tolerance in health and disease.Frontiers in immunology · 2022Review
- An adjuvant-containing cDC1-targeted recombinant fusion vaccine conveys strong protection against murine melanoma growth and metastasis.Oncoimmunology · 2022Article
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The fate of tissue-resident memory CD4 T cells (Trm) has been incompletely investigated. Here we show that intranasal, but not parenteral, immunization with CTA1-3M2e-DD stimulated M2e-specific Th17 Trm cells, which conferred strong protection against influenza virus infection in the lung. These cells rapidly expanded upon infection and effectively restricted virus replication as determined by CD4 T cell depletion studies. Single-cell RNAseq transcriptomic and TCR VDJ-analysis of M2e-tetramer-sorted CD4 T cells on day 3 and 8 post infection revealed complete Th17-lineage dominance (no Th1 or Tregs) with extensive functional diversity and expression of gene markers signifying mature resident Trm cells (Cd69, Nfkbid, Brd2, FosB). Unexpectedly, the same TCR clonotype hosted cells with different Th17 subcluster functions (IL-17, IL-22), regulatory and cytotoxic cells, suggesting a tissue and context-dependent differentiation of reactivated Th17 Trm cells. A gene set enrichment analysis demonstrated up-regulation of regulatory genes (Lag3, Tigit, Ctla4, Pdcd1) in M2e-specific Trm cells on day 8, indicating a tissue damage preventing function. Thus, contrary to current thinking, lung M2e-specific Th17 Trm cells are sufficient for controlling infection and for protecting against tissue injury. These findings will have strong implications for vaccine development against respiratory virus infections and influenza virus infections, in particular.
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