Circadian rhythm disruption exacerbates Th2‐like immune response in murine allergic airway inflammation

Abstract

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.

Circadian rhythm regulates the function of immune cells and participates in the development of tumors

“…Circadian rhythms have a significant impact on Th17 cells beyond CD4 Tn cells. A study found that circadian rhythm disorder (CRD) contributes to the development of allergic rhinitis (AR) by affecting Th2 and Th17 immune responses [ 103 ]. Levels of IL-4, IL-6, IL-13, and IL-17A significantly increased in CRD + AR patients, while IFN-γ levels decreased [ 103 ].…”

Melatonin in food allergy: Mechanism and potential therapy

“…The disease severities of many immune‐mediated and allergic diseases show a 24‐h pattern, for example, allergic rhinitis, 155 bronchial asthma, 156 and atopic eczema 157 . Severe allergic symptoms are often accompanied by sleep disorders, which are associated with abnormal circadian rhythmicity, including loss of rhythmic secretions of melatonin 36,158 .…”

“…Severe allergic symptoms are often accompanied by sleep disorders, which are associated with abnormal circadian rhythmicity, including loss of rhythmic secretions of melatonin 36,158 . Additionally, disruption of clock activity exacerbates the severity of allergic reactions and increases susceptibility to allergic diseases 9,156 . For example, sleep deprivation significantly reduces the threshold of reactivities in people with peanut allergies, putting them at a greater risk of allergic reactions 9 .…”

“…36,158 Additionally, disruption of clock activity exacerbates the severity of allergic reactions and increases susceptibility to allergic diseases. 9,156 For example, sleep deprivation significantly reduces the threshold of reactivities in people with peanut allergies, putting them at a greater risk of allergic reactions. 9 The components of the circadian clock interact with critical elements and pathways of immune responses, proliferation, and metabolism of gut microbiota, as well as epithelial barrier functions, thereby regulating the oscillatory allergic reactions.…”

Tight Junctions, the Epithelial Barrier, and Toll-like Receptor-4 During Lung Injury

“…Results from additional studies on the role of clock genes in lung pathophysiology are highlighted in a published article by Sundar et al [116]. Disruption of circadian rhythm in a mouse model decreases the expression of occludin and ZO-1 levels in respiratory mucosa [117]. The expression of TJ proteins occludin, ZO-1, and claudins has also been shown to be under circadian control in the intestine, retina, kidney, and brain [118][119][120][121].…”