CD11b+ myeloid cells are the key mediators of Th2 cell homing into the airway in allergic inflammation

J Immunol. 2009 Jan 1;182(1):623-35. doi: 10.4049/jimmunol.182.1.623.

Abstract

STAT6-mediated chemokine production in the lung is required for Th2 lymphocyte and eosinophil homing into the airways in allergic pulmonary inflammation, and thus is a potential therapeutic target in asthma. However, the critical cellular source of STAT6-mediated chemokine production has not been defined. In this study, we demonstrate that STAT6 in bone marrow-derived myeloid cells was sufficient for the production of CCL17, CCL22, CCL11, and CCL24 and for Th2 lymphocyte and eosinophil recruitment into the allergic airway. In contrast, STAT6 in airway-lining cells did not mediate chemokine production or support cellular recruitment. Selective depletion of CD11b(+) myeloid cells in the lung identified these cells as the critical cellular source for the chemokines CCL17 and CCL22. These data reveal that CD11b(+) myeloid cells in the lung help orchestrate the adaptive immune response in asthma, in part, through the production of STAT6-inducible chemokines and the recruitment of Th2 lymphocytes into the airway.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bone Marrow Transplantation / immunology
  • Bone Marrow Transplantation / pathology
  • CD11b Antigen / biosynthesis*
  • Cells, Cultured
  • Chemokine CCL17 / biosynthesis
  • Chemokine CCL22 / biosynthesis
  • Chemokine CCL24 / biosynthesis
  • Chemotaxis, Leukocyte / immunology*
  • Disease Models, Animal
  • Immunity, Innate
  • Inflammation / immunology
  • Inflammation / metabolism
  • Inflammation / pathology
  • Lung / immunology*
  • Lung / metabolism
  • Lung / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Mice, Transgenic
  • Myeloid Cells / immunology*
  • Myeloid Cells / metabolism
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Respiratory Hypersensitivity / immunology*
  • Respiratory Hypersensitivity / metabolism
  • Respiratory Hypersensitivity / pathology*
  • STAT6 Transcription Factor / deficiency
  • STAT6 Transcription Factor / genetics
  • STAT6 Transcription Factor / physiology*
  • Th2 Cells / immunology*
  • Th2 Cells / pathology
  • Th2 Cells / transplantation

Substances

  • CD11b Antigen
  • Ccl17 protein, mouse
  • Ccl22 protein, mouse
  • Ccl24 protein, mouse
  • Chemokine CCL17
  • Chemokine CCL22
  • Chemokine CCL24
  • STAT6 Transcription Factor
  • Stat6 protein, mouse
  • Ovalbumin