Abstract
The salivary gland is rhythmically controlled by sympathetic nerve activation from the suprachiasmatic nucleus (SCN), which functions as the main oscillator of circadian rhythms. In humans, salivary IgA concentrations reflect circadian rhythmicity, which peak during sleep. However, the mechanisms controlling this rhythmicity are not well understood. Therefore, we examined whether the timing of parasympathetic (pilocarpine) or sympathetic (norepinephrine; NE) activation affects IgA secretion in the saliva. The concentrations of saliva IgA modulated by pilocarpine activation or by a combination of pilocarpine and NE activation were the highest in the middle of the light period, independent of saliva flow rate. The circadian rhythm of IgA secretion was weakened by an SCN lesion and Clock gene mutation, suggesting the importance of the SCN and Clock gene on this rhythm. Adrenoceptor antagonists blocked both NE- and pilocarpine-induced basal secretion of IgA. Dimeric IgA binds to the polymeric immunoglobulin receptor (pIgR) on the basolateral surface of epithelial cells and forms the IgA-pIgR complex. The circadian rhythm of Pigr abundance peaked during the light period, suggesting pIgR expression upon rhythmic secretion of IgA. We speculate that activation of sympathetic nerves during sleep may protect from bacterial access to the epithelial surface through enhanced secretion of IgA.
Highlights
Mammals possess circadian clock systems that control various physiological phenomena such as body temperature, sleep-wake cycles, and liver metabolism[1, 2]
We investigated whether salivary IgA secretion reflects circadian rhythms
We observed a significant increase in IgA concentration during the light phase in the NE group, but not in the control group, as assessed by one-way ANOVA and Kruskal-Wallis test (Fig. 1a,d, Supplemental Table S1)
Summary
Mammals possess circadian clock systems that control various physiological phenomena such as body temperature, sleep-wake cycles, and liver metabolism[1, 2]. Circadian clock systems are organized by a central clock called the suprachiasmatic nuclei (SCN)[3], and by peripheral clocks located in many peripheral organs[4, 5] In addition to this system, biological functions of metabolism and the immune system are known to affect circadian rhythms[6, 7]. Rhythmical Clock gene expression in the salivary gland is controlled by sympathetic activation via the SCN17. Both mRNA and protein expression of adrenoceptors in the submandibular glands were reported to show circadian rhythm[18, 19]. We aimed to investigate how sympathetic nerve activation affects salivary IgA secretion rhythms through control of the biological clock
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