Dendritic cells in allergic airway inflammation.

Dendritic cells (DCs) are primary antigen-presenting cells involved in interactions with T cells leading to the proliferation of TH1 or TH2 cell types. In asthma, predominance of TH2 cells appears to be responsible for disease pathogenesis. Differentiation of TH2 cells is driven by a variety of factors such as the expression of high levels of costimulatory molecules, the cytokine profile, and the subset of DCs. Many inflammatory cells involved in the pathogenesis of asthma either directly or indirectly modulate DC function. Traditional treatments for asthma decrease the number of airway DCs in animals as well as in patients with asthma. Immunomodulators including interleukin (IL)-10, transforming growth factor (TGF)-beta, cytosine-phosphate-guanosine-containing oligodeoxynucleotides (CpG-ODN), 1alpha,25-dihydroxyvitamin D3, and fetal liver tyrosine kinase 3 ligand (Flt3L) are involved in the modulation of the function of DCs. Based on the critical review of the interaction between DCs and other inflammatory cells, we propose that activation of T cells by DCs and sensitization to inhaled allergen and resulting airway inflammation are dependent on plasmacytoid and myeloid subset of lung DCs to induce an immune response or tolerance and are tightly regulated by T-regulatory cells. Effects of various therapeutic agents to modulate the function of lung myeloid DCs have been discussed.