IL-33 induces antigen-specific IL-5+ T cells and promotes allergic-induced airway inflammation independent of IL-4

Kurowska-Stolarska, M. et al. (2008) IL-33 induces antigen-specific IL-5+ T cells and promotes allergic-induced airway inflammation independent of IL-4. Journal of Immunology, 181(7), pp. 4780-4790.

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Type 2 cytokines (IL-4, IL-5, and IL-13) play a pivotal role in helminthic infection and allergic disorders. CD4+ T cells which produce type 2 cytokines can be generated via IL-4-dependent and -independent pathways. Although the IL-4-dependent pathway is well documented, factors that drive IL-4-independent Th2 cell differentiation remain obscure. We report here that the new cytokine IL-33, in the presence of Ag, polarizes murine and human naive CD4+ T cells into a population of T cells which produce mainly IL-5 but not IL-4. This polarization requires IL-1R-related molecule and MyD88 but not IL-4 or STAT6. The IL-33-induced T cell differentiation is also dependent on the phosphorylation of MAPKs and NF-κB but not the induction of GATA3 or T-bet. In vivo, ST2−/− mice developed attenuated airway inflammation and IL-5 production in a murine model of asthma. Conversely, IL-33 administration induced the IL-5-producing T cells and exacerbated allergen-induced airway inflammation in wild-type as well as IL-4−/− mice. Finally, adoptive transfer of IL-33-polarized IL-5+IL-4−T cells triggered airway inflammation in naive IL-4−/− mice. Thus, we demonstrate here that, in the presence of Ag, IL-33 induces IL-5-producing T cells and promotes airway inflammation independent of IL-4.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Liew, Prof Foo and Xu, Dr Damo and Murphy, Dr Grace and Komai-Koma, Dr Mousa and Li, Mr Yubin and Pitman, Dr Nick and Kurowska-Stolarska, Professor Mariola
Authors: Kurowska-Stolarska, M., Kewin, P., Murphy, G., Russo, R. C., Stolarski, B., Garcia, C. C., Komai-Koma, M., Pitman, N., Li, Y., McKenzie, A. N. J., Teixeira, M. M., Liew, F. Y., and Xu, D.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Journal of Immunology
Journal Abbr.:J. Immunol.
Publisher:American Association of Immunologists
ISSN (Online):1550-6606
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
380241Toll-like receptors on T cellsFoo LiewMedical Research Council (MRC)G9818261/69296Infection Immunity and Inflammation Medicine
486461The role of IL-35 in infection and inflammationFoo LiewMedical Research Council (MRC)G0801198III -IMMUNOLOGY