| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom; and
Division of Immunology, Infection, and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, United Kingdom
IL-33 (IL-1F11) binds ST2 (IL-1R4), both of which are associated with optimal CD4+ Th2 polarization. Exogenous IL-33 drives induction of Th2-associated cytokines and associated pathological changes within the gut mucosa. Th2 polarization is also a prerequisite to expulsion of the intestinal-dwelling nematode Trichuris muris. In this study, we demonstrate that IL-33 mRNA is expressed early during parasite infection and susceptible mice can be induced to expel the parasite by a regime of exogenous IL-33 administration. IL-33 prevents an inappropriate parasite-specific Th1-polarized response and induces IL-4, IL-9, and IL-13. This redirection requires the presence of T cells and must occur at the initiation of the response to the pathogen. Interestingly, exogenous IL-33 also induced thymic stromal lymphopoietin mRNA within the infected caecum, an epithelial cell-restricted cytokine essential for the generation of Th2-driven parasite immunity. IL-33 also acts independently of T cells, altering intestinal pathology in chronically infected SCID mice, leading to an increased crypt length and intestinal epithelial cell proliferation, but reducing goblet cell hyperplasia. Thus, the ability of IL-33 to induce Th2 responses has functional relevance in the context of intestinal helminth infection, particularly during the initiation of the response.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 Studies performed at University of Manchester were supported by Medical Research Council Grant 71672 and Wellcome Trust Grant 064820, and at the University of Glasgow by Medical Research Council Grant 69296 and Wellcome Trust Grant 080217.
2 Address correspondence and reprint requests to Dr. Richard K. Grencis, Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, United Kingdom, M13 9PT. E-mail address: richard.k.grencis{at}manchester.ac.uk or Dr. Foo Y. Liew, Division of Immunology, Infection, and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, 120 University Place, Glasgow G12 8TA, United Kingdom. E-mail address: f.y.liew{at}clinmed.gla.ac.uk
3 Abbreviations used in this paper: TSLP, thymic stromal lymphopoietin; CBA, cytometric bead array kit; DC, dendritic cell; ES, excretory/secretory; HPRT, hypoxanthine phosphoribosyltransferase; IEC, intestinal epithelial cell; IKK, I
B kinase; MLN, mesenteric lymph node; p.i., postinfection.
This article has been cited by other articles:
|
|
 |
|
  L. Guo, G. Wei, J. Zhu, W. Liao, W. J. Leonard, K. Zhao, and W. Paul IL-1 family members and STAT activators induce cytokine production by Th2, Th17, and Th1 cells PNAS, August 11, 2009; 106(32): 13463 - 13468. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. C. Taylor, C. Zaph, A. E. Troy, Y. Du, K. J. Guild, M. R. Comeau, and D. Artis TSLP regulates intestinal immunity and inflammation in mouse models of helminth infection and colitis J. Exp. Med., March 16, 2009; 206(3): 655 - 667. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Pecaric-Petkovic, S. A. Didichenko, S. Kaempfer, N. Spiegl, and C. A. Dahinden Human basophils and eosinophils are the direct target leukocytes of the novel IL-1 family member IL-33 Blood, February 12, 2009; 113(7): 1526 - 1534. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kurowska-Stolarska, P. Kewin, G. Murphy, R. C. Russo, B. Stolarski, C. C. Garcia, M. Komai-Koma, N. Pitman, Y. Li, A. N. J. McKenzie, et al. IL-33 Induces Antigen-Specific IL-5+ T Cells and Promotes Allergic-Induced Airway Inflammation Independent of IL-4 J. Immunol., October 1, 2008; 181(7): 4780 - 4790. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Hudson, G. P. Christophi, R. C. Gruber, J. R. Wilmore, D. A. Lawrence, and P. T. Massa Induction of IL-33 expression and activity in central nervous system glia J. Leukoc. Biol., September 1, 2008; 84(3): 631 - 643. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Xu, H.-R. Jiang, P. Kewin, Y. Li, R. Mu, A. R. Fraser, N. Pitman, M. Kurowska-Stolarska, A. N. J. McKenzie, I. B. McInnes, et al. IL-33 exacerbates antigen-induced arthritis by activating mast cells PNAS, August 5, 2008; 105(31): 10913 - 10918. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
