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Th2 Differentiation Is Unaffected by Jagged2 Expression on Dendritic Cells¹

Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104

Expression of the Jagged Notch ligands by dendritic cells (DCs) has been suggested to play a role in instructing Th2 responses. Supporting this hypothesis, we found that Jagged2 but not Jagged1 expression, correlates with the ability of DCs to induce Th2 responses. Jagged2 expression is up-regulated in response to the helminth soluble Schistosoma mansoni egg Ag, which conditions DCs to induce Th2 responses, and is markedly down-regulated following exposure to TLR agonists that generally promote Th1 responses. Conversely, Jagged1 expression is markedly induced by TLR ligation. Despite these correlations, suppression of expression of Jagged2 using retrovirally delivered small interfering RNA failed to affect the ability of DCs to induce Th2 cell differentiation either in vitro or in vivo. Moreover, retrovirally induced expression of Jagged2 did not enhance the ability of DCs to induce Th2 cell responses. Our data indicate that Jagged2 expression by DCs is not sufficient or required for Th2 cell differentiation.

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 This work was supported by Grant AI53825 from the National Institutes of Health (to E.J.P.). E.J.P. is a Burroughs Wellcome Fund Scholar in Molecular Parasitology. C.M.K. is supported by the Canadian Institutes of Health Research and the International Human Frontier Science Program Organization.

² Current address: Merck Research Laboratories, Department of Biochemistry and Molecular Biology, Merck Frosst Canada and Company, Kirkland, Quebec, Canada.

³ Current address: Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, VA 22908.

⁴ Address correspondence and reprint requests to Dr. Edward J. Pearce, Department of Pathobiology, 318 Hill Pavilion, School of Veterinary Medicine, University of Pennsylvania, 380 South University Avenue, Philadelphia PA 19104-4539. E-mail address: ejpearce{at}mail.med.upenn.edu

⁵ Abbreviations used in this paper: DC, dendritic cell; SEA, soluble Schistosoma mansoni egg Ag; LLO, listeriolysin O; CT, cholera toxin; ICS, intracellular staining; IRES, internal ribosomal entry site sequence.

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