HIF1α Deficiency in Dendritic Cells Attenuates Symptoms and Inflammatory Indicators of Allergic Rhinitis in a SIRT1-Dependent Manner

Abstract

Background: Allergic rhinitis is the most prevalent atopic disorder worldwide. Inflammation is believed to participate in allergic rhinitis. Previous studies indicate that hypoxia-inducible factor (HIF) promotes the development of allergic rhinitis, and dendritic cells are also involved in allergic rhinitis. Methods:We explored the consequences of HIF1α deficiency in dendritic cells on allergic rhinitis. Allergic rhinitis in mice was induced by ovalbumin (OVA). The levels of IgE, leukotriene C4 (LTC4), eosinophil cationic protein (ECP), prostaglandin D2 (PGD2), IFN-γ, IL-2, IL-4, IL-5, IL-10, and IL-13 in serum or nasal lavage fluid (NLF) were detected by ELISA. Inflammatory cells in NLF were counted by hemocytometer. The protein levels of p-ERK1/2, p-p38, p-JNK2, SIRT1, p-IκBα, and p65 were determined by Western blot. Results:HIF1α deficiency in dendritic cells (HIF1α^CD11c–/–) decreased sneezing and nasal rubbing, the production of OVA-specific IgE, LTC4, and ECP in serum and NLF, and the numbers of leukocytes, eosinophils, lymphocytes, and neutrophils in NLF. Th1 cytokines increased, while Th2 cytokines decreased in HIF1a^CD11c–/– mice. SIRT1/NF-κB signaling was inhibited in HIF1α^CD11c–/– mice, while SIRT1 inhibitor administration in HIF1α^CD11c–/– mice attenuated the symptoms and inflammatory indicators of allergic rhinitis. Conclusion:HIF1α deficiency in dendritic cells attenuates symptoms and inflammatory indicators of allergic rhinitis in a SIRT1-dependent manner.