Unique functions of the type 11 interleukin 4 receptor identified in mice lacking the interleukin 13 receptor alpha 1 chain

The interleukin 4 receptor (IL-4R) is a central mediator of T helper type 2 (T(H)2)-mediated disease and associates with either the common gamma-chain to form the type I IL-4R or with the IL-13R alpha 1 chain (IL-13R alpha 1) to form the type II IL-4R. Here we used II13ral(-/-) mice to characterize the distinct functions of type I and type II IL-4 receptors in vivo. In contrast to II4ra(-/-) mice, which have weak T(H)2 responses, II13ra1(-/-) mice had exacerbated T(H)2 responses. II13ra1(-/-) mice showed much less mortality after infection with Schistosoma mansoni and much more susceptibility to Nippostrongylus brasiliensis. IL-13R alpha 1 was essential for allergen-induced airway hyperreactivity and mucus hypersecretion but not for fibroblast or alternative macrophage activation. Thus, type I and II IL-4 receptors exert distinct effects on immune responses.