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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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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