Background: Dendritic cells (DCs) are essential for the initiation and maintenance of T(H)2 responses to inhaled antigen that lead to the establishment of allergic diseases. Two subpopulations of nonplasmacytoid DCs (ie, CD11b(low)CD103+ and CD11b(high)CD103(-)) are found in lung/airway tissues. Yet the identification and migratory properties of the DC subset that contributes to T(H)2-mediated responses remain to be clarified. CD47, a signal regulatory protein (SIRP)-alpha partner, reportedly governed skin DC migration.
Objective: We here thought to investigate the role of CD47/SIRP-alpha interactions in airway DC trafficking and the development of allergic airway inflammation.
Methods: We characterized the DC influx into lungs and mediastinal lymph nodes in CD47(-/-) and CD47(+/+) BALB/c mice by using experimental models of allergic asthma. Mice were systemically (intraperitoneal ovalbumin/alum) or locally (intratracheal ovalbumin-loaded bone marrow-derived DCs) immunized and challenged by ovalbumin aerosol. We also evaluated the consequences of SIRP-alpha-Fc fusion molecule administration on the induction of airway disease in BALB/c mice.
Results: SIRP-alpha selectively identified the CD11b(high)CD103(-) DC subset that predominantly accumulated in mediastinal lymph nodes during airway inflammation. However, CD103(-)SIRP-alpha+ DC trafficking, T(H)2 responses, and airway disease were impaired in CD47(-/-) mice. Importantly, the adoptive transfer of CD103(-) SIRP-alpha+CD47(+/+) but not CD47(-/-) DCs elicited a strong T(H)2 response in CD47(-/-) mice. Finally, the administration of SIRP-alpha-Fc molecule protected BALB/c mice from allergic airway inflammation.
Conclusion: Lung CD11b(high)CD103(-)SIRP-alpha+ DC migration is governed by self-CD47 expression, and manipulation of the CD47/SIRP-alpha pathway suppresses CD103(-)SIRP-alpha(+) DC-driven pathogenic T(H)2 responses and airway inflammation.
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