Dendritic cells: pulmonary immune regulation and asthma

Dendritic cells (DCs) may play a pivotal role in the initiation and establishment of chronic T-helper cell (Th)-2 mediated lung inflammation as seen in asthma. Current in vitro data indicate that the haemopoietic lineage of the DC or the local environment in which a DC matures, or both acting together, can instruct the DC to become a Th1- or Th2-inducing antigen-presenting cell. Once allergen-specific Th2 memory cells are drawn into the lung, repeated allergen presentation by lung DCs may drive the persistent stimulation of allergen-specific memory Th2 cells and precipitate a state of chronic inflammation that contributes to the remodelling and hyperreactive airways that characterize asthma. In addition, the persistent stimulation of effector Th2 cells and the subsequent Th2 cytokine secretion can create a Th2 cytokine milieu in the lung that may influence the differentiation of antigen-specific Th0 in the lung and naive Th in the lung-associated lymph nodes to develop into Th2 effector cells. Immunoglobulin E receptors on antigen-presenting cells may facilitate chronic T-helper cell-2 inflammation directly by focusing allergen to dendritic cells for uptake and indirectly by stimulating alveolar macrophages to secrete mediators that lead to the maturation of dendritic cells with a low capacity to secrete interleukin-12.