Absence of the Type I IL-4 Receptor reduces IFNγ production and increases the severity of airway inflammation in an ovalbumin induced model of asthma (55.8)

Abstract The TH2 cytokines, IL-4 and IL-13, play critical roles in inducing allergic lung inflammation and also drive alternative activation of macrophages (AAM). Although both cytokines share receptor subunits and signaling proteins, there is evidence that IL-4 and IL-13 have differential roles in asthma pathogenesis. While important in TH2 differentiation, the contribution of IL-4 signaling via the Type I receptor, in modulating airway inflammation remains unclear. Here, we adoptively transferred wild-type ova primed CD4+ T cells into C57BL/6, Rag2KO, or gamma c (γc) KO mice. γcKO mice developed increased peribronchial and perivascular inflammation in the lungs upon ova challenge, compared to WT and Rag2KO mice. Moreover, significantly higher numbers of eosinophils were present in the bronchoalveolar lavage (BAL) and lung tissue in γcKO mice. Characteristic AAM proteins FIZZ1 and YM1 were expressed in lung epithelial cells in both mouse strains, but greater intensity of YM1 expression was observed in γcKOs. The number of FIZZ1+ or YM1+ airways was also significantly higher in these mice. It is known that γcKO mice lack NK cells; Type I R signaling in NK cells induces IFNγ production. Indeed, we found reduced secretion of IFNγ in the BAL in γcKO mice as compared to Rag2KO mice. These results suggest that the Type I R acts to suppress allergic lung inflammation through IFNγ production and, in the presence of TH2 effectors, the Type II R can mediate allergic responses in its absence.