Scavenger Receptors and Resistance to Inhaled Allergens
Annual rept. 17 Jan 2006-16 Jan 2007
HARVARD UNIV CAMBRIDGE MA
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After OVA sensitization and aerosol challenge, SR-AIII and MARCO-deficient mice exhibited greater eosinophilic airway inflammation and airway hyper responsiveness compared to wild-type mice. A role for simple SRA-mediated antigen clearance scavenging by lung macrophages was excluded by observation of comparable uptake of fluorescent OVA by wild-type and SRA-deficient lung Mphis and DCs. In contrast, airway instillation of fluorescent antigen revealed significantly higher traffic of labelled DCs to thoracic lymph nodes in SRA-deficient mice than in controls. The increased migration of SRA-deficient DCs was accompanied by enhanced proliferation in thoracic lymph nodes of adoptively transferred OVA-specific T cells after airway OVA challenge. The data identify a novel role for SRAs expressed on lung DCs in down-regulation of specific immune responses to aero-allergens by reduction of DC migration from the site of antigen uptake to the draining lymph nodes.
- Medicine and Medical Research