Dynamics of Dendritic Cell Phenotype and Interactions with CD4+ T Cells in Airway Inflammation and Tolerance

Abstract

An emerging concept is that different types of dendritic cells (DCs) initiate different immune outcomes, such as tolerance vs inflammation. In this study, we have characterized the DCs from the lung draining lymph nodes of mice immunized for allergic airway inflammation or tolerance and examined their interactions with CD4+ T cells. The DC population derived from tolerized mice was predominantly CD11c+, B220+, Gr-1+, CD11b−, and MHC class IIlow, which resembled plasmacytoid-type DCs whereas DCs from the inflammatory condition were largely CD11c+, B220−, Gr-1−, CD11b+, and MHC class IIhigh resembling myeloid-type DCs. The DCs from the tolerogenic condition were poor inducers of T cell proliferation. DCs from both conditions induced T cell IL-4 production but the T cells cultured with tolerogenic DCs were unresponsive to IL-4 as indicated by inhibition of STAT6 activation and expression of growth factor-independent 1, which has been recently shown to be important for STAT6-activated Th2 cell expansion. Our data suggest that airway tolerance vs inflammation is determined by the DC phenotype in lung draining lymph nodes.

Simvastatin promotes Th2-type responses through the induction of the chitinase family member Ym1 in dendritic cells

“…Overall, the morphology of the simvastatin-treated DCs was similar to the description of murine and human pDCs as we and others have described (ref. 20; Fig. 1B).…”

Origin and functional specializations of DC subsets in the lung

“…The precise subset of DC performing this tolerogenic role remains a matter of debate. Some investigators could show that tolerance induction and formation of Treg depends on an intact pDC system [9,36,37]. Others found that tolerance also required cDC that migrated to the MLN in a CCR7-dependent manner [38,39].…”

“…We and others have shown that pDC have an important role in inhalation tolerance and homeostasis in the lung. After administering OVA protein, pDC of the MLN take up OVA, but in contrast to lung-derived cDC, pDC are very poor at presenting OVA to CD4 1 T cells [9,37]. However, when pDC were specifically depleted using antibodies, inhalation tolerance to OVA no longer occurred and mice developed features of severe asthma, even in the total absence of any adjuvant.…”

Activation of Pulmonary Dendritic Cells and Th2-Type Inflammatory Responses on Instillation of Engineered, Environmental Diesel Emission Source or Ambient Air Pollutant Particles in vivo

“…The lung is known to benefit from the functions of two major subsets of DC, termed conventional myeloid DC (mDC), that express moderate to high levels of both CD11c+ and CD11b+, and a second subpopulation, termed plasmacytoid DC (pDC), that display cell-surface expression of PDCA-1 and low levels of CD11c [23][24][25][26][27] . Studies exploring the role of DC activation and allergic risk in asthma development have focused on the adjuvant potential of PM to induce allergic sensitization to a coadministered antigen-like ovalbumin (OVA) or house dust mite [6,12,18,[28][29][30][31][32] .…”