Epitopes described in "Age-related increases in PGD(2) expression impair respiratory DC migration, resulting in diminished T cell responses upon respiratory virus infection in mice."

Article Authors:Jincun Zhao; Jingxian Zhao; Kevin Legge; Stanley Perlman
Article Title:Age-related increases in PGD(2) expression impair respiratory DC migration, resulting in diminished T cell responses upon respiratory virus infection in mice.
Reference Detail
Reference ID:1025986
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.
Affiliations:Department of Microbiology, University of Iowa, Iowa City, Iowa 52242, USA.
Reference Type:Literature
PubMed ID:22105170
Journal:J Clin Invest
Journal Volume:121
Article Pages:4921-30
Journal ISSN:0021-9738
Article Chemical List:Ccr7 protein, mouse;Prostaglandin Antagonists;Receptors, CCR7;Prostaglandin D2
Article MeSH List:Aging(metabolism); Animals; Cell Movement(drug effects); Cellular Microenvironment(immunology); Coronavirus Infections(immunology; metabolism; virology); Dendritic Cells(immunology; pathology); Disease Susceptibility; Immunocompromised Host; Influenza A virus(immunology); Lung(immunology; pathology); Lymph Nodes(immunology; pathology); Lymphocyte Activation; Mice; Mice, Inbred C57BL; Murine hepatitis virus(immunology); Orthomyxoviridae Infections(immunology; metabolism; virology); Prostaglandin Antagonists(pharmacology; therapeutic use); Prostaglandin D2(biosynthesis; physiology); Receptors, CCR7(biosynthesis; genetics); Respiratory Syncytial Virus Infections(immunology; metabolism; virology); Respiratory Syncytial Viruses(immunology); SARS Virus(immunology); Severe Acute Respiratory Syndrome(immunology; metabolism; virology); Specific Pathogen-Free Organisms; T-Lymphocyte Subsets(immunology)
Curation Last Updated:2015-07-30 20:47:46