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Scavenger Receptors SR-AI/II and MARCO limit pulmonary dendritic cell migration and allergic airway inflammation

Mohamed S Arredouani1, Francesca Franco, Amy Imrich

  • 1Department of Environmental Health, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|April 20, 2007
PubMed

Insights

Scavenger receptors (SR-As) on lung dendritic cells normally limit allergic airway inflammation. Removing SR-As increases allergic responses by allowing more dendritic cell migration to lymph nodes.

Area of Science:

  • Immunology
  • Allergy Research
  • Innate Immunity

Background:

  • Class A scavenger receptors (SR-As), including MARCO and SR-AI/II, are expressed on lung macrophages and dendritic cells.
  • These receptors play a role in innate immune defenses against inhaled pathogens and particles.
  • Increased SR-A expression in an OVA-asthma model suggested a role in allergen response modulation.

Purpose of the Study:

  • To investigate the role of SR-As in modulating immune responses to inhaled allergens.
  • To determine if SR-As influence allergic airway inflammation and hyperresponsiveness.
  • To elucidate the mechanism by which SR-As might regulate immune cell trafficking and T cell proliferation.

Main Methods:

  • Utilized a murine model of ovalbumin (OVA)-induced asthma.
  • Compared wild-type mice with mice deficient in SR-AI/II and MARCO.
  • Assessed airway inflammation, airway hyperresponsiveness, antigen uptake by lung cells, dendritic cell migration, and T cell proliferation.

Main Results:

  • SR-AI/II and MARCO-deficient mice showed increased eosinophilic airway inflammation and hyperresponsiveness after OVA challenge.
  • Antigen uptake by lung macrophages and dendritic cells was comparable between wild-type and SR-A-deficient mice.
  • SR-A-deficient mice exhibited significantly higher dendritic cell traffic to thoracic lymph nodes and enhanced T cell proliferation.

Conclusions:

  • SR-As expressed on lung dendritic cells play a novel role in down-regulating specific immune responses to aeroallergens.
  • This regulation is achieved by reducing dendritic cell migration from the antigen uptake site to draining lymph nodes.
  • Targeting SR-As could offer a therapeutic strategy for allergic airway diseases.

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