Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Eosinophilia / immunology
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Female
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Goblet Cells / pathology
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Granuloma, Respiratory Tract / immunology
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Granuloma, Respiratory Tract / pathology
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Immunoglobulin E / biosynthesis
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Interleukin-13 / genetics
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Interleukin-13 / physiology*
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Interleukin-4 / genetics
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Interleukin-4 / physiology*
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Interleukin-5 / genetics
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Interleukin-5 / physiology*
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Interleukin-9 / genetics
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Interleukin-9 / physiology*
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Kinetics
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Mastocytosis / immunology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Nippostrongylus
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Pregnancy
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Strongylida Infections / immunology
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Strongylida Infections / parasitology
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Strongylida Infections / pathology
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Survival Analysis
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Th2 Cells / immunology*
Substances
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Interleukin-13
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Interleukin-5
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Interleukin-9
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Interleukin-4
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Immunoglobulin E