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* Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
Biomedical Research Institute, Rockville, MD 20852;
Department of Inflammation, Amgen, Seattle, WA 98119; and
Immunology Program, Benaroya Research Institute, Seattle, WA 98101
Thymic stromal lymphopoietin was recently identified as a master switch for the development of allergen-driven Th2 responses. However, the role of thymic stromal lymphopoietin (TSLP) in the development of helminth-induced Th2 responses is unclear. Here, using TSLPR–/– mice, we show that while TSLPR signaling participates in the development of Schistosoma mansoni egg-induced CD4+ Th2 responses, it plays only a transient role in the development of Th2-dependent pathology in the lung, liver, and intestine. Studies conducted in a pulmonary granuloma model showed that while a reduction in IL-4/IL-13-dependent granulomatous inflammation and tissue eosinophilia was observed in TSLPR–/– mice undergoing a primary response, lesion formation was not affected during a secondary granulomatous response, even though IL-5 and IL-13 were modestly reduced in the knockout mice. To evaluate the importance of TSLPR signaling in the development of a chronic Th2-dependent response, TSLPR–/– mice were also infected with S. mansoni cercariae. Here, the only significant difference noted in TSLPR–/– mice was a modest decrease in liver fibrosis in acutely infected animals. The transient decrease in fibrosis was associated with increased production of the antifibrotic cytokine IFN-
and decreased production of the profibrotic cytokine IL-13. Although the altered cytokine response persisted in chronically infected TSLPR–/– mice, it failed to reduce granuloma formation or fibrosis, confirming that TSLPR signaling plays a limited role in the development of chronic Th2-dependent pathology. Collectively, these findings suggest that while TSLPR signaling serves a key role in allergen-driven Th2 responses, it exerts minor regulatory activity during this chronic helminth infection.
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1 This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases (to T.A.W.) and by National Institutes of Health Grants AI068731 and AR056113 (to S.F.Z.).
2 T.R.R. and J.T.P. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Thomas A. Wynn, Immunopathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, 50 South Drive, Room 6154, Mail Stop Code 8003, Bethesda, MD 20892. E-mail address: twynn{at}niaid.nih.gov
4 Abbreviations used in this paper: TSLP, thymic stromal lymphopoietin; DC, dendritic cell; MFI, mean fluorescence intensity; WT, wild type.
This article has been cited by other articles:
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  R. M. Maizels, E. J. Pearce, D. Artis, M. Yazdanbakhsh, and T. A. Wynn Regulation of pathogenesis and immunity in helminth infections J. Exp. Med., September 28, 2009; 206(10): 2059 - 2066. [Abstract] [Full Text] [PDF]
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 J. C. Massacand, R. C. Stettler, R. Meier, N. E. Humphreys, R. K. Grencis, B. J. Marsland, and N. L. Harris Helminth products bypass the need for TSLP in Th2 immune responses by directly modulating dendritic cell function PNAS, August 18, 2009; 106(33): 13968 - 13973. [Abstract] [Full Text] [PDF]
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