Impaired Lymph-Node Homing of Dendritic Cells (DC) in Allergen-Challenged Surfactant Protein D Deficient (SP-D-/-) Mice is Associated with Lack of Ccr7 and Reduced Expression of Signal Regulatory Protein-Alpha (Sirp-945;)

L.R. Forbes AFFILIATIONS Children's Hospital of Philadelphia, Philadelphia, PA University of Pennsylvania, Philadelphia, PA , C. Koziol-White, B. Ducka, M. Fehrenbach, A. Haczku

Author address: 

Children’s Hospital of Philadelphia, Philadelphia, PA, University of Pennsylvania, Philadelphia, PA.

Abstract: 

RATIONALE: We previously showed that the immunoprotective epithelial molecule, SP-D, constitutively engages SIRP-α on the surface of pulmonary innate immune cells. SIRP-α has been implicated in lymph-node homing of DC. We hypothesized that myeloid DC accumulation in the airways of SP-D-/- mice is due, at least partly, to a failure of lymph node-directed DC migration. METHODS: Wild-type (wt) and SPD-/- mice received sensitization and challenge with Aspergillus fumigatus (Af) and were i.v. injected with a phagocyte label, PKH-26. Bronchoalveolar lavage fluid (BAL) was harvested before (0h), 24h and 96h after Af inhalation. Immunohistochemistry and multicolor FACS analysis was used to assess BAL CD11b+/CD11c+/MHC-II+ DC for expression of SIRP-α , Ccr4 (mediates epithelial migration) and Ccr7 (mediates lymph node homing). RESULTS: Bone-marrow derived (CD11b+) phagocytic (PKH+), Ccr4+ DC gradually accumulated up to 96h after Af inhalation. The number of Ccr7+ DC peaked at 24h but disappeared from the airways by 96h after Af suggesting a lymph-node directed efflux. Lack of SP-D resulted in increased numbers of myeloid DC in the airways and decreased DC recovery from the thoracic lymph nodes. In comparison with wt, SP-D-/- DC had strikingly diminished Ccr7 expression 24h after Af challenge. This was associated with a reduced SIRP-α + cells in the BAL of SP-D-/- mice. CONCLUSIONS: Migration of activated myeloid DC to the epithelium is followed by lymph node homing of the Ccr7+ cells after Af challenge. We propose that an impaired lymph node homing of DC in SP-D-/- mice is due to lack of SIRP-α ligation and inability to express Ccr7.
2011

abstract No: 

AB270

Full conference title: 

American Academy of Allergy Asthma & Immunology
    • AAAAI 2011 (67th)