Abstract
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<sup>−/−</sup> mice, we show that while TSLPR signaling participates in the development of <i>Schistosoma mansoni</i> egg-induced CD4<sup>+</sup> 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<sup>−/−</sup> 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<sup>−/−</sup> mice were also infected with <i>S. mansoni</i> cercariae. Here, the only significant difference noted in TSLPR<sup>−/−</sup> 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-γ and decreased production of the profibrotic cytokine IL-13. Although the altered cytokine response persisted in chronically infected TSLPR<sup>−/−</sup> 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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