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

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 (HIF1αCD11c-/-) 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 HIF1aCD11c-/- mice. SIRT1/NF-κB signaling was inhibited in HIF1αCD11c-/- mice, while SIRT1 inhibitor administration in HIF1αCD11c-/- 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.