Unique functions of the type II interleukin 4 receptor identified in mice lacking the interleukin 13 receptor alpha1 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 alpha1 chain (IL-13Ralpha1) to form the type II IL-4R. Here we used Il13ra1-/- mice to characterize the distinct functions of type I and type II IL-4 receptors in vivo. In contrast to Il4ra-/- mice, which have weak T(H)2 responses, Il13ra1-/- mice had exacerbated T(H)2 responses. Il13ra1-/- mice showed much less mortality after infection with Schistosoma mansoni and much more susceptibility to Nippostrongylus brasiliensis. IL-13Ralpha1 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.
Ramalingam
Thirumalai R
TR
Laboratory of Parasitic Diseases, National institutes of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA.
Pesce
John T
JT
Sheikh
Faruk
F
Cheever
Allen W
AW
Mentink-Kane
Margaret M
MM
Wilson
Mark S
MS
Stevens
Sean
S
Valenzuela
David M
DM
Murphy
Andrew J
AJ
Yancopoulos
George D
GD
Urban
Joseph F
JF
Donnelly
Raymond P
RP
Wynn
Thomas A
TA
D000485:Allergens / Q000276:immunology; D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000276:immunology; D002478:Cells, Cultured; D004198:Disease Susceptibility; D005347:Fibroblasts / Q000276:immunology; D053661:Interleukin-13 Receptor alpha1 Subunit / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009093:Mucus / Q000378:metabolism; D009559:Nippostrongylus / Q000502:physiology; D053659:Receptors, Interleukin-4, Type II / Q000502:physiology*; D012550:Schistosoma mansoni / Q000276:immunology / Q000502:physiology; D012555:Schistosomiasis mansoni / Q000276:immunology / Q000401:mortality; D017206:Strongylida Infections / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D000485:Allergens; D000947:Antigens, Helminth; D053661:Interleukin-13 Receptor alpha1 Subunit; D053659:Receptors, Interleukin-4, Type II