Journal article
Age-related increases in PGD 2 expression impair respiratory DC migration, resulting in diminished T cell responses upon respiratory virus infection in mice
The Journal of clinical investigation, Vol.121(12), pp.4921-4930
12/2011
DOI: 10.1172/JCI59777
PMID: 22105170
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.
Details
- Title: Subtitle
- Age-related increases in PGD 2 expression impair respiratory DC migration, resulting in diminished T cell responses upon respiratory virus infection in mice
- Creators
- Jincun ZhaoJingxian ZhaoKevin LeggeStanley Perlman
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.121(12), pp.4921-4930
- DOI
- 10.1172/JCI59777
- PMID
- 22105170
- NLM abbreviation
- J Clin Invest
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Publisher
- American Society for Clinical Investigation
- Language
- English
- Date published
- 12/2011
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
- Record Identifier
- 9983777469202771
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