IL-4 induces characteristic Th2 responses even in the combined absence of IL-5, IL-9, and IL-13.
Functional redundancy is highly prevalent among the Th2 interleukins (IL)-4, IL-5, IL-9, and IL-13. To define the critical functions of these cytokines, we have generated a novel panel of compound Th2 cytokine-deficient mice (from single to quadruple cytokine knockouts). We find that these Th2 cytokines are not essential for fetal survival even during allogeneic pregnancy. Using intestinal parasite infection and a pulmonary granuloma model, we demonstrate cryptic roles for IL-4, IL-5, IL-9, and IL-13 in these responses. Significantly, although IL-5, IL-9, and IL-13 add to the speed and magnitude of the response, a threshold is reached at which IL-4 alone can activate all Th2 effector functions. These mice reveal distinct spatial, temporal, and hierarchical cytokine requirements in immune function.
Fallon
Padraic G
PG
Immunomodulation Group, Department of Biochemistry, Trinity College, Dublin 2, Ireland.
Jolin
Helen E
HE
Smith
Philippa
P
Emson
Claire L
CL
Townsend
Michael J
MJ
Fallon
Rosie
R
Smith
Philip
P
McKenzie
Andrew N J
AN
D000818:Animals; D000831:Animals, Newborn; D004802:Eosinophilia / Q000276:immunology; D005260:Female; D020397:Goblet Cells / Q000473:pathology; D015769:Granuloma, Respiratory Tract / Q000276:immunology / Q000473:pathology; D007073:Immunoglobulin E / Q000096:biosynthesis; D018793:Interleukin-13 / Q000235:genetics / Q000502:physiology*; D015847:Interleukin-4 / Q000235:genetics / Q000502:physiology*; D015848:Interleukin-5 / Q000235:genetics / Q000502:physiology*; D016906:Interleukin-9 / Q000235:genetics / Q000502:physiology*; D007700:Kinetics; D008415:Mastocytosis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009559:Nippostrongylus; D011247:Pregnancy; D017206:Strongylida Infections / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D016019:Survival Analysis; D018418:Th2 Cells / Q000276:immunology*
D018793:Interleukin-13; D015848:Interleukin-5; D016906:Interleukin-9; D015847:Interleukin-4; D007073:Immunoglobulin E