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Background: Chronic jet lag (CJL)-induced circadian rhythm disruption (CRD) is positively correlated with an increased risk of allergic diseases. However, little is known about the mechanism involved in allergic rhinitis (AR)., Methods: Aberrant light/dark cycles-induced CRD mice were randomly divided into negative control (NC) group, AR group, CRD+NC group, and CRD+AR group (n = 8/group). After ovalbumin (OVA) challenge, nasal symptom scores were recorded. The expression of Occludin and ZO-1 in both nasal mucosa and lung tissues was detected by reverse transcription-quantitative polymerase chain reaction (RT-PCR) and immunohistochemical staining. The level of OVA-specific immunoglobulin E (sIgE) and T-helper (Th)-related cytokines in the plasma was measured by enzyme-linked immunosorbent assay (ELISA), and the proportion of Th1, Th2, Th17, and regulatory T cell (Treg) in splenocytes was evaluated by flow cytometry., Results: The nasal symptom score in the CRD+AR group was significantly higher than those in the AR group with respect to eosinophil infiltration, mast cell degranulation, and goblet cell hyperplasia. The expression of ZO-1 and Occludin in the nasal mucosa and lung tissues in the CRD+AR group were significantly lower than those in the AR group. Furthermore, Th2 and Th17 cell counts from splenocytes and OVA-sIgE, interleukin 4 (IL-4), IL-6, IL-13, and IL-17A levels in plasma were significantly increased in the CRD+AR group than in the AR group, whereas Th1 and Treg cell count and interferon γ (IFN-γ) level were significantly decreased in the CRD+AR group., Conclusion: CRD experimentally mimicked CJL in human activities, could exacerbate local and systemic allergic reactions in AR mice, partially through decreasing Occludin and ZO-1 level in the respiratory mucosa and increasing Th2-like immune response in splenocytes., (© 2021 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Background: Allergic rhinitis (AR) symptoms exhibit prominent 24-hour variations associated with the biological clock. Although endogenous glucocorticoids synchronize circadian oscillator in the nasal mucosa, the precise mechanism of AR remains unclear. Therefore, using a mouse model, we investigated the association between circadian-clock genes and AR symptoms at various time-points., Methods: Based on the rhythmic secretion of corticosterone levels, we chose 2 time-points, ZT4 (10:00 AM) and ZT16 (10:00 PM), to observe dynamic changes of nasal symptoms, immunologic responses, and circadian-clock gene period (Per) expressions., Results: In the AR group, nasal symptom scores at ZT4 were significantly higher than at ZT16, with a greater increase in eosinophils, mast cells, and total immunoglobulin E levels at ZT4. The scores had a negative correlation with fluctuation of corticosterone levels. T-helper 1 (Th1) cell counts and interferon-γ levels decreased significantly at ZT4 compared with ZT16 in the AR group, whereas Th2 cells; Th17 cells; and interleukin (IL)-4, -13, and -17A levels increased significantly at ZT4 compared with ZT16. Furthermore, Per2 gene expression levels were attenuated at ZT4 and elevated at ZT16, but correlated negatively with Th2 and Th17 responses associated with Gata3 and Rorγt expression levels that were enhanced at ZT4 and reduced at ZT16 in the AR group., Conclusion: Our results suggest that the Per2 gene may influence diurnal variations of AR symptom severity, partially through its possible anti-inflammatory effect on the circadian regulation of GATA3 and RORγt levels in immune cells. This further demonstrates the neural-immune-endocrinal mechanism of circadian rhythm in AR and sheds new light on chronotherapeutic approaches to AR., (© 2020 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)