Interleukin-17D (IL-17D) belongs to the IL-17 family of cytokines. While the members of the IL-17 family have been implicated in inflammation and host defense, the function of IL-17D remains unclear. Here, we showed that the lack of IL-17D expression confers protection against
Listeria
infection. A deficiency in IL-17D also resulted in less weight loss with reduced pathogen burden during influenza A virus infection. During infection, the loss of IL-17D resulted in compromised CD8 T cell activity. CD8 T cell depletion in IL-17D-deficient mice restored the bacterial burden to a level similar to that found in WT mice. Similarly, IL-17D-deficient mice in a RAG-deficient background had no difference in bacterial and viral burden compared to WT mice. IL-17D controlled CD8 T cell activity in part by suppressing the function of dendritic cells. We found that IL-17D from the non-hematopoietic compartment regulates protective immunity during infection. Together, our data led to the identification of IL-17D as a critical cytokine during intracellular bacteria and virus infection that suppresses the activity of CD8 T cells by regulating dendritic cells.
Background: Cancer stem cells (CSCs) have been proposed to be responsible for tumor recurrence and chemoresistance. Previous studies suggested that miR-153 played essential roles in lung cancer. However, the molecular mechanism of miR-153 in regulating the stemness of non-small cell lung cancer (NSCLC) remains poorly understood. In this study, we investigated the role of miR-153 in regulation of the stemness of NSCLC. Methods: The stemness property of lung stem cancer cells was detected by sphere formation assay, immunofluorescence, and Western blot. Luciferase reporter assay was performed to investigate the direct binding of miR-153 to the 3′-UTR of JAG1 mRNA. Animal study was conducted to evaluate the effect of miR-153 on tumor growth in vivo. The clinical relevance of miR-153 in NSCLC was evaluated by Rt-PCR and Kaplan-Meier analysis. Results: MiR-153 expression was decreased in lung cancer tissues. Reduced miR-153 expression was associated with lung metastasis and poor overall survival of lung cancer patients. Jagged1, one of the ligands of Notch1, is targeted by miR-153 and inversely correlates with miR-153 in human lung samples. More importantly, we found that miR-153 inhibited stem cell-like phenotype and tumor growth of lung adenocarcinoma through inactivating the Jagged1/Notch1 axis. Conclusion: MiR-153 suppresses the stem cell-like phenotypes and tumor growth of lung adenocarcinoma by targeting Jagged1 and provides a potential therapeutic target in lung cancer therapy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.