Chemokines in allergic asthma

The recognition of two major classes of helper T cells, Th1 and Th2, has focused attention on the distinctive sets of cytokines produced by these cells and on their role in activating or suppressing inflammatory responses. More recently, it has become clear that Th1 and Th2 cells also differ with respect to the chemokine receptors they express, a finding that may help explain the different timing of their entry into inflamed tissues. Now, Panina-Bordignon and coworkers have studied the expression of chemokines and chemokine receptors in the inflamed airways of asthmatic subjects. They find that two Th2-restricted chemokine receptors, CCR4 and CCR8, are upregulated in the asthmatic lung following challenge with inhaled allergens. Several chemokines that bind CCR4 are also induced under these circumstances, suggesting a mechanism by which Th2 cells are activated to infiltrate the mucosa of the lung. Although the known CCR8-specific chemokines are not induced, the authors find that the number of CCR8-positive cells correlates with the severity of the asthmatic response, so this receptor may well be important in this disease pathway. The induction of CCR4 and its ligands appears to be specific for atopic disease, since a similar pattern is seen in atopic dermatitis but not in chronic obstructive pulmonary disease, which is thought to be driven by Th1 responses.