Abstract
The mechanisms that initiate T helper type 2 (T(H)2) responses are poorly understood. Here we demonstrate that cysteine protease-induced T(H)2 responses occur via 'cooperation' between migratory dermal dendritic cells (DCs) and basophils positive for interleukin 4 (IL-4). Subcutaneous immunization with papain plus antigen induced reactive oxygen species (ROS) in lymph node DCs and in dermal DCs and epithelial cells of the skin. ROS orchestrated T(H)2 responses by inducing oxidized lipids that triggered the induction of thymic stromal lymphopoietin (TSLP) by epithelial cells mediated by Toll-like receptor 4 (TLR4) and the adaptor protein TRIF; by suppressing production of the T(H)1-inducing molecules IL-12 and CD70 in lymph node DCs; and by inducing the DC-derived chemokine CCL7, which mediated recruitment of IL-4(+) basophils to the lymph node. Thus, the T(H)2 response to cysteine proteases requires DC-basophil cooperation via ROS-mediated signaling.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Vesicular Transport / metabolism
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Animals
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Antigens / immunology
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Basophils / immunology
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Basophils / metabolism*
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Basophils / pathology
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Cell Communication
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Cytokines / biosynthesis*
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Cytokines / genetics
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Epithelial Cells / immunology
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Epithelial Cells / metabolism
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Epithelial Cells / pathology
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Interleukin-4 / biosynthesis
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Langerhans Cells / immunology
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Langerhans Cells / metabolism*
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Langerhans Cells / pathology
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Lymphocyte Activation
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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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Mice, Transgenic
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Papain / immunology
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Reactive Oxygen Species / immunology
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Reactive Oxygen Species / metabolism*
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Signal Transduction
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Th2 Cells / immunology*
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Thymic Stromal Lymphopoietin
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Toll-Like Receptor 4 / metabolism
Substances
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Adaptor Proteins, Vesicular Transport
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Antigens
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Cytokines
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Reactive Oxygen Species
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TICAM-1 protein, mouse
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Toll-Like Receptor 4
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Interleukin-4
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Papain
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Thymic Stromal Lymphopoietin
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TSLP protein, mouse