Th2-induced airway mucus production is dependent on IL-4R alpha, but not on eosinophils

Mucus hyperproduction in asthma results from airway inflammation and contri butes to clinical symptoms, airway obstruction, and mortality. In human ast hmatics and in animal models, excess mucus production correlates with airwa y eosinophilia. We previously described a system in which TCR transgenic CD 4 Th2 cells generated in vitro were transferred into recipient mice and act ivated in the respiratory tract with inhaled Ag, Th2 cells stimulated airwa y eosinophilia and a marked increase in mucus production, while mice that r eceived Th1 cells exhibited airway inflammation without eosinophilia or muc us. Mucus could be induced by IL-4(-/-) Th2 cells at comparable levels to m ucus induced by IL-4(+/+) Th2 cells. In the current studies we dissect furt her the mechanisms of Th2-induced mucus production. When IL-4(-/-) Th2 cell s are transferred into IL-4R alpha(-/-) mice, mucus is not induced, and BAL eosinophilia is absent. These data suggest that in the absence of IL-4, IL -13 may be critical for Th2-induced mucus production and eosinophilia. To d etermine whether eosinophils are important in mucus production, IL-5(-/-) T h2 cells were transferred into IL-5(-/-) recipients. Eosinophilia was aboli shed, yet mucus staining in the epithelium persisted. These studies show de finitively that IL-5, eosinophils, or mast cells are not essential, but sig naling through IL-4R alpha is critically important in Th2 cell stimulation of mucus production.