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- Title
The T helper type 2 response to cysteine proteases requires dendritic cell–basophil cooperation via ROS-mediated signaling.
- Authors
Hua Tang; Weiping Cao; Kasturi, Sudhir Pai; Ravindran, Rajesh; Nakaya, Helder I.; Kundu, Kousik; Murthy, Niren; Kepler, Thomas B.; Malissen, Bernard; Pulendran, Bali
- Abstract
The mechanisms that initiate T helper type 2 (TH2) responses are poorly understood. Here we demonstrate that cysteine protease–induced TH2 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 TH2 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 TH1-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 TH2 response to cysteine proteases requires DC-basophil cooperation via ROS-mediated signaling.
- Publication
Nature Immunology, 2010, Vol 11, Issue 7, p608
- ISSN
1529-2908
- Publication type
Academic Journal
- DOI
10.1038/ni.1883