Eosinophil recruitment is dynamically regulated by interplay among lung dendritic cell subsets after allergen challenge

Nat Commun. 2018 Sep 24;9(1):3879. doi: 10.1038/s41467-018-06316-9.

Abstract

Eosinophil infiltration, a hallmark of allergic asthma, is essential for type 2 immune responses. How the initial eosinophil recruitment is regulated by lung dendritic cell (DC) subsets during the memory stage after allergen challenge is unclear. Here, we show that the initial eosinophil infiltration is dependent on lung cDC1s, which require nitric oxide (NO) produced by inducible NO synthase from lung CD24-CD11b+ DC2s for inducing CCL17 and CCL22 to attract eosinophils. During late phase responses after allergen challenge, lung CD24+ cDC2s inhibit eosinophil recruitment through secretion of TGF-β1, which impairs the expression of CCL17 and CCL22. Our data suggest that different lung antigen-presenting cells modulate lung cDC1-mediated eosinophil recruitment dynamically, through secreting distinct soluble factors during the memory stage of chronic asthma after allergen challenge in the mouse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / immunology
  • Animals
  • Asthma / immunology*
  • Chemokine CCL17 / immunology
  • Chemokine CCL17 / metabolism
  • Chemokine CCL22 / immunology
  • Chemokine CCL22 / metabolism
  • Chronic Disease
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Disease Models, Animal
  • Eosinophils / immunology*
  • Female
  • Humans
  • Lung / cytology
  • Lung / immunology
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Papain / immunology
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Allergens
  • Ccl17 protein, mouse
  • Ccl22 protein, mouse
  • Chemokine CCL17
  • Chemokine CCL22
  • Tgfb1 protein, mouse
  • Transforming Growth Factor beta1
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Papain