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T Cell Immunity in Emerging Respiratory Viral Infections: Mechanisms, Dysregulation, and Therapeutic Targets

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: 30 September 2026 | Viewed by 443

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Guest Editor
Department of Microbiology & Immunology, Center for Predictive Medicine, University of Louisville, Louisville, KY 40202, USA
Interests: pathogenesis of respiratory virus-related symptoms and age-related immune dysregulation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Coronavirus, influenza virus and other emerging respiratory virus infections induce activation of acute and chronic immune responses, to which T cells—both innate (such as gamma delta T cells, NK T cells and ILCs) and adaptive (alpha/beta T cells) subsets—make indispensable contributions. T cell-mediated protective effects can be realized by secreting anti-viral cytokines or immune cell-recruiting chemokines, killing infected cells, as well as regulating inflammation caused by infection. Compared to virus-specific antibodies, virus-specific T cells recognize conserved epitopes of viruses, thus favoring the elimination and control of immune-escaping variants, such as SARS-CoV-2 variants of concern. Despite intensive interest in identifying virus-specific T cells and their contributions to disease prevention and control, the mechanisms underlying the generation, regulation and maintenance of coronavirus-induced T cell responses remain to be further clarified. On the other hand, dysregulated T cell-mediated responses may lead to excessive tissue damage and represent potential targets for treating immunopathology caused by coronavirus infection, especially in highly susceptible populations, such as the elderly and those with co-morbidities. Finally, severe respiratory viral infections, especially SARS-CoV-2, have been found to cause T cell lymphopenia and dysfunction, which serve as important indicators for predicting disease prognosis and therapeutic targets in both human patients and animal models. Clarifying the role of T cells and their effects during both the acute and chronic phases of respiratory viral infection is urgently needed to develop next-generation strategies to prevent and treat virus-associated respiratory diseases.

Dr. Jian Zheng
Guest Editor

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Keywords

  • T cell
  • coronavirus
  • immune memory
  • immunopathogenesis
  • aging

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Published Papers (1 paper)

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Review

22 pages, 3937 KB  
Review
Phospholipase A2 Isoforms in Lung Immunity and Respiratory Infections: Potential Targets for Next-Generation Therapy
by Shweta Joshi, Kelly Walter, Dante Hamiel, Divyasha Saxena and Jian Zheng
Int. J. Mol. Sci. 2026, 27(11), 4740; https://doi.org/10.3390/ijms27114740 - 25 May 2026
Viewed by 190
Abstract
Despite the critical role of lipid-mediated signaling in regulating host immunity, endorsed by growing evidence, the interaction between lipid metabolism and immune response remains largely unknown. This review aims to elucidate the immunomodulatory role of a lung-enriched lipid metabolic pathway mediated by the [...] Read more.
Despite the critical role of lipid-mediated signaling in regulating host immunity, endorsed by growing evidence, the interaction between lipid metabolism and immune response remains largely unknown. This review aims to elucidate the immunomodulatory role of a lung-enriched lipid metabolic pathway mediated by the phospholipase A2 (PLA2) family, which comprises a diverse range of lipid-hydrolyzing enzymes. Based on their location, structure, substrate specificity and physiological roles, PLA2s can be classified into secreted PLA2s (sPLA2s), cytosolic PLA2s (cPLA2s), calcium-independent PLA2s (iPLA2s), and lysosomal-associated PLA2s (lPLA2s). These PLA2 isoforms are similar in that they can all cleave cellular membrane-associated phospholipids, releasing free lysophospholipids and fatty acids such as arachidonic acid, which subsequently serve as precursors for a wide range of bioactive mediators responsible for physiological functions and pathological changes. Respiratory infections, especially those caused by bacteria and viruses, represent a substantial threat to the health of the population worldwide and cause billions of disease cases and millions of deaths annually. Respiratory infections provoke airway inflammation, characterized by increased vascular permeability and the influx of immune cells, resulting in tissue damage, impaired gas exchange, acute respiratory distress syndrome (ARDS) and even death. During infections and inflammatory milieu, airway-expressed PLA2 can further increase and exhibit protection by restricting pathogens and inflammation or, in contrast, exacerbate the pathogenesis. In this manuscript, we will provide an overview of the current knowledge on the biological functions of PLA2 isoforms, especially concerning membrane-associated isoforms in respiratory infections, and offer insight into the spatial and temporal regulation of immune responses mediated by PLA2 and the subsequent modulation of host–pathogen interactions and the balance between protective effects and pathological outcomes. Full article
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