International Immunology Advance Access originally published online on June 11, 2008
International Immunology 2008 20(8):1019-1030; doi:10.1093/intimm/dxn060
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IL-33 amplifies both Th1- and Th2-type responses through its activity on human basophils, allergen-reactive Th2 cells, iNKT and NK Cells
Department of Inflammation Research, Amgen Inc., 1201 Amgen Court West, Seattle, WA, USA
Correspondence to: D. E. Smith; E-mail: smithde{at}amgen.com
IL-33 is an IL-1 family member recently identified as the ligand for T1/ST2 (ST2), a member of the IL-1 receptor family. ST2 is stably expressed on mast cells and Th2 effector T cells and its function has been studied in the context of Th2-associated inflammation. Indeed, IL-33 induces Th2 cytokines from mast cells and polarized mouse T cells and leads to pulmonary and mucosal Th2 inflammation when administered in vivo. To better understand how this pathway modulates inflammatory responses, we examined the activity of IL-33 on a variety of human immune cells. Human blood-derived basophils expressed high levels of ST2 receptor and responded to IL-33 by producing several pro-inflammatory cytokines including IL-1β, IL-4, IL-5, IL-6, IL-8, IL-13 and granulocyte macrophage colony-stimulating factor. Next, utilizing a human Th2-polarized T cell culture system derived from allergic donor blood cells, we found that IL-33 was able to enhance antigen-dependent and -independent T cell responses, including IL-5, IL-13 and IFN-
production. IL-33 activity was also tested on V
24-positive human invariant NKT (iNKT) cells. In the presence of -galactosylceramide antigen presentation, IL-33 dose dependently enhanced iNKT production of several cytokines, including both IL-4 and IFN-. IL-33 also directly induced IFN- production from both iNKT and human NK cells via cooperation with IL-12. Taken together, these results indicate that in addition to its activity on human mast cells, IL-33 is capable of activating human basophils, polarized T cells, iNKT and NK cells. Moreover, the nature of the responses elicited by IL-33 suggests that this axis may amplify both Th1- and Th2-oriented immune responses.
Keywords: cytokines, inflammation, NK cells, Th1/Th2 cells
Transmitting editor: Sergio Romagnani
Received 6 February 2008, accepted 16 May 2008.
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