Murine Th9 cells promote the survival of myeloid dendritic cells in cancer immunotherapy
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Dendritic cells (DCs) are professional antigen-presenting cells to initiate immune responses, and DC survival time is important for affecting the strength of T-cell responses. Interleukin (IL)-9-producing T-helper (Th)-9 cells play an important role in anti-tumor immunity. However, it is unclear how Th9 cells communicate with DCs. In this study, we investigated whether murine Th9 cells affected the survival of myeloid DCs. DCs derived from bone marrow of C57BL/6 mice were cocultured with Th9 cells from OT-II mice using transwell, and the survival of DCs was examined. DCs cocultured with Th9 cells had longer survival and fewer apoptotic cells than DCs cultured alone in vitro. In melanoma B16-OVA tumor-bearing mice, DCs conditioned by Th9 cells lived longer and induced stronger anti-tumor response than control DCs did in vivo. Mechanistic studies revealed that IL-3 but not IL-9 secreted by Th9 cells was responsible for the prolonged survival of DCs. IL-3 upregulated the expression of anti-apoptotic protein Bcl-xL and activated p38, ERK and STAT5 signaling pathways in DCs. Taken together, our data provide the first evidence that Th9 cells can promote the survival of DCs through IL-3, and will be helpful for designing Th9 cell immunotherapy and more effective DC vaccine for human cancers.
KeywordsTh9 cells Dendritic cells Survival IL-3 Cancer immunotherapy
5(6)-Carboxyfluorescein diacetate succinimidyl ester
Granulocyte–macrophage colony-stimulating factor
Phorbol myristate acetate
Transforming growth factor
Tumor necrosis factor
This work was supported by grants from the National Cancer Institute (R01 CA96569, R01 CA103978, R01 CA138402 and P50 CA142509), the Leukemia & Lymphoma Society and Multiple Myeloma Research Foundation.
Conflict of interest
The authors declare no competing financial interests.
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