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The T helper type 2 response to cysteine proteases requires dendritic cell-basophil cooperation via ROS-mediated signaling.


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.

SUBMITTER: Tang H 

PROVIDER: S-EPMC3145206 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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The T helper type 2 response to cysteine proteases requires dendritic cell-basophil cooperation via ROS-mediated signaling.

Tang Hua H   Cao Weiping W   Kasturi Sudhir Pai SP   Ravindran Rajesh R   Nakaya Helder I HI   Kundu Kousik K   Murthy Niren N   Kepler Thomas B TB   Malissen Bernard B   Pulendran Bali B  

Nature immunology 20100523 7


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 tr  ...[more]

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