Circadian clock-dependent increase in salivary IgA secretion modulated by sympathetic receptor activation in mice

Sci Rep. 2017 Aug 18;7(1):8802. doi: 10.1038/s41598-017-09438-0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Glands / metabolism
  • Adrenal Glands / pathology
  • Adrenergic Fibers / drug effects
  • Adrenergic Fibers / immunology
  • Adrenergic Fibers / metabolism
  • Animals
  • CLOCK Proteins / genetics
  • CLOCK Proteins / metabolism
  • Circadian Clocks*
  • Circadian Rhythm
  • Immunoglobulin A, Secretory / biosynthesis*
  • Immunoglobulin A, Secretory / immunology
  • Male
  • Mice
  • Mice, Knockout
  • Receptors, Cell Surface / metabolism*
  • Saliva / immunology*
  • Salivary Glands / immunology
  • Salivary Glands / metabolism
  • Suprachiasmatic Nucleus / physiology


  • Immunoglobulin A, Secretory
  • Oscar protein, mouse
  • Receptors, Cell Surface
  • CLOCK Proteins