Absence of the Type I IL-4 receptor increases the severity of airway inflammation in a murine model of asthma (141.6)

Abstract

Abstract The TH2 cytokines, IL-4 and IL-13, play critical roles in inducing allergic lung inflammation, eosinophilia, mucus hypersecretion and also drive alternative activation of macrophages (AAM). Although both cytokines share receptor subunits and signaling machinery, it is becoming apparent that IL-4 and IL-13 have differential roles in asthma pathogenesis. While clearly important in TH2 differentiation, the contribution of IL-4 signaling via the Type I receptor in allergic responses remains unclear. Here, we adoptively transferred wild-type ova primed CD4+ T cells into C57BL/6, Rag2KO, or gamma c (γc) KO mice. We found that γc KO mice developed increased inflammation around the airways and blood vessels in the lungs upon ova challenge when compared to WT and Rag2KO mice. Moreover, significantly higher numbers of eosinophils were present in the bronchoalveolar lavage (BAL) and lung tissue in γc KO mice. Immunohistochemical studies showed that all mouse strains expressed characteristic AAM proteins FIZZ1 and YM1 in lung epithelial cells, while macrophages expressed only YM1. Interestingly, γc KO mice had high levels of FIZZ1 protein in their BAL at baseline, which dropped sharply upon ova treatment. These results suggest that the Type I R acts to suppress allergic lung inflammation and, in the presence of TH2 effectors, the Type II R can mediate allergic responses in its absence. Further experiments are required to fully elucidate the role of the Type I IL-4R and γc in asthma.