Pulmonary stromal cells induce the generation of regulatory DC attenuating T-cell-mediated lung inflammation

Eur J Immunol. 2008 Oct;38(10):2751-61. doi: 10.1002/eji.200838542.

Abstract

The tissue microenvironment may affect the development and function of immune cells such as DC. Whether and how the pulmonary stromal microenvironment can affect the development and function of lung DC need to be investigated. Regulatory DC (DCreg) can regulate T-cell response. We wondered whether such regulatory DC exist in the lung and what is the effect of the pulmonary stromal microenvironment on the generation of DCreg. Here we demonstrate that murine pulmonary stromal cells can drive immature DC, which are regarded as being widely distributed in the lung, to proliferate and differentiate into a distinct subset of DCreg, which express high levels of CD11b but low levels of MHC class II (I-A), CD11c, secrete high amounts of IL-10, NO and prostaglandin E2 (PGE2) and suppress T-cell proliferation. The natural counterpart of DCreg in the lung with similar phenotype and regulatory function has been identified. Pulmonary stroma-derived TGF-beta is responsible for the differentiation of immature DC to DCreg, and DCreg-derived PGE2 contributes to their suppression of T-cell proliferation. Moreover, DCreg can induce the generation of CD4+CD25+Foxp3+ Treg. Importantly, infusion with DCreg attenuates T-cell-mediated eosinophilic airway inflammation in vivo. Therefore, the pulmonary microenvironment may drive the generation of DCreg, thus contributing to the maintenance of immune homoeostasis and the control of inflammation in the lung.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dinoprostone / biosynthesis
  • Dinoprostone / immunology
  • Eosinophils / immunology
  • Lung / immunology*
  • Lung / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Pneumonia / immunology*
  • Stromal Cells / cytology
  • Stromal Cells / immunology*
  • Stromal Cells / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / metabolism

Substances

  • Transforming Growth Factor beta
  • Dinoprostone