Cited by 268Immunotherapy and Immune ResponsesT-cell and B-cell ImmunologyAsthma and respiratory diseases

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Age-related increases in PGD2 expression impair respiratory DC migration, resulting in diminished T cell responses upon respiratory virus infection in mice

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Zhao, Jincun, Zhao, Jingxian, Legge, Kevin, Perlman, Stanley·2011·Journal of Clinical Investigation

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Abstract

The morbidity and mortality associated with respiratory virus infection is felt most keenly among the elderly. T cells are necessary for viral clearance, and many age-dependent intrinsic T cell defects have been documented. However, the development of robust T cell responses in the lung also requires respiratory DCs (rDCs), which must process antigen and migrate to draining LNs (DLNs), and little is known about age-related defects in these T cell-extrinsic functions. Here, we show that increases in prostaglandin D(2) (PGD(2)) expression in mouse lungs upon aging correlate with a progressive impairment in rDC migration to DLNs. Decreased rDC migration resulted in diminished T cell responses and more severe clinical disease in older mice infected with respiratory viruses. Diminished rDC migration associated with virus-specific defects in T cell responses and was not a result of cell-intrinsic defect, rather it reflected the observed age-dependent increases in PGD(2) expression. Blocking PGD(2) function with small-molecule antagonists enhanced rDC migration, T cell responses, and survival. This effect correlated with upregulation on rDCs of CCR7, a chemokine receptor involved in DC chemotaxis. Our results suggest that inhibiting PGD(2) function may be a useful approach to enhance T cell responses against respiratory viruses in older humans.

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“…immune evasion by SARS-CoV-2 may limit T cell priming (Blanco-Melo et al., 2020; Vabret et al., 2020), and there is the possibility of fewer professional antigen presenting cells in the lungs with advanced age, as has been seen in small animal models of SARS (Chen et al., 2010; Zhao et al., 2011).”

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Authors: Zhao, J., Zhao, J., Legge, K., & Perlman, S.
Affiliations: University of Iowa (US)
Corresponding author: Perlman, Stanley
ORCID: Zhao, Jincun
Zhao, Jingxian
Legge, Kevin
Perlman, Stanley
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2011-12-01
Volume: 121
Issue: 12
Pages: 4921-4930
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci59777
PMC: PMC3226008
OpenAlex: W2115101593
Cited by: 265
References: 60
Citations by year: 2026: 8 · 2025: 11 · 2024: 8 · 2023: 15 · 2022: 26 · 2021: 42 · 2020: 66 · 2019: 5 · 2018: 10 · 2017: 12 · 2016: 14 · 2015: 9 · 2014: 15 · 2013: 16 · 2012: 6
FWCI: 5.68
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (PO1AI060699, AI060699, AI071085)
National Institute of Allergy and Infectious Diseases (R01AI071085, R56 AI79424, R01AI091322, R56AI079424, P01AI060699)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
Keywords: prostaglandin D2, dendritic cell migration, aging, respiratory viral infections, T cell response, draining lymph nodes, CCR7, chemokine receptors, age-related immunosenescence, lung immunity
MeSH terms: Aging, Animals, Cell Movement, Dendritic Cells, Disease Susceptibility, Murine hepatitis virus, Lung, Lymph Nodes, Lymphocyte Activation, Mice, Inbred C57BL, Orthomyxoviridae Infections, Influenza A virus, Prostaglandin Antagonists, Respiratory Syncytial Viruses, Specific Pathogen-Free Organisms, Prostaglandin D2, T-Lymphocyte Subsets, Immunocompromised Host, Coronavirus Infections, Respiratory Syncytial Virus Infections, Severe Acute Respiratory Syndrome, Severe acute respiratory syndrome-related coronavirus, Mice, Receptors, CCR7, Cellular Microenvironment

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Age-related increases in PGD2 expression impair respiratory DC migration, resulting in diminished T cell responses upon respiratory virus infection in mice

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