Critical role for syndecan-4 in dendritic cell migration during development of allergic airway inflammation

Abstract

Syndecan-4 (SDC4), expressed on dendritic cells (DCs) and activated T cells, plays a crucial role in DC motility and has been shown as a potential target for activated T-cell-driven diseases. In the present study, we investigate the role of SDC4 in the development of T-helper 2 cell-mediated allergic asthma. Using SDC4-deficient mice or an anti-SDC4 antibody we show that the absence or blocking of SDC4 signalling in ovalbumin-sensitized mice results in a reduced asthma phenotype compared with control animals. Most importantly, even established asthma is significantly decreased using the anti-SDC4 antibody. The disturbed SDC4 signalling leads to an impaired motility and directional migration of antigen-presenting DCs and therefore, to a modified sensitization leading to diminished airway inflammation. Our results demonstrate that SDC4 plays an important role in asthma induction and indicate SDC4 as possible target for therapeutic intervention in this disease.

Syndecans in Inflammation at a Glance

“…The blocking of syndecan-4 in ovalbumin sensitized mice resulted in a reduced inflammation due to the defective migration of antigen presenting dendritic cells. This affects the Th2 derived immune response where dendritic cells failed to deliver signals to Th2 cells (40).…”

Maternal phthalate exposure promotes allergic airway inflammation over 2 generations through epigenetic modifications

“…Lung resistance was measured by using invasive plethysmography in response to inhaled methacholine, as described previously [23][24][25] and in more detail in the Methods section in this article's Online Repository.…”

Scaffolding protein Gab1 regulates myeloid dendritic cell migration in allergic asthma

“…Dendritic cells (DCs), the most potent antigen-presenting cells (APCs), play an essential role in allergic asthma by inducing Th2 immunity to inhaled allergens. Following persistent antigen uptake and recognition, respiratory DCs are recruited and migrate to draining lymph nodes (DLNs), activating naive T cells and initiating the adaptive immune response [7,8]. Thus, there is an urgent need to elucidate the molecular mechanisms controlling DCs in asthmatic inflammation.…”