Affiliations: Johann Friedrich Blumenbach Institute of Zoology and Anthropology, University of Göttingen, Göttingen, Germany
Correspondence to: Rüdiger Hardeland, Johann Friedrich Blumenbach Institute of Zoology and Anthropology, University of Göttingen, Bürgerstr. 50, 37073 Göttingen, Germany. Tel.: +49 551 395414; E-mail: [email protected].
Abstract: The circadian oscillator system is known to affect various immune functions. These actions can be attributed to either direct effects of oscillator components, including those present in peripheral cellular clocks, or to indirect actions via strongly rhythmic regulators such as melatonin and glucocorticoids. The aim of this article is to outline the connections between circadian and immune systems at the level of regulation by noncoding RNAs. Numerous pleiotropically acting miRNAs are summarized that display functions in both systems. Many miRNAs that regulate inflammation are shown to harbor putative or demonstrated binding sites for oscillator components in their respective promoters or to be under control of melatonin or glucocorticoids. Melatonin, which possesses immune modulatory properties, has been shown to act partially via upregulation of sirtuin-1, a regulator that participates in inflammation control and also increases circadian amplitudes. Thus, both melatonin and sirtuin-1 can be regarded as connecting factors between circadian and immune systems. Additional bridging effects can be expected from other noncoding RNAs, in particular, circRNAs and rhythmically expressed lncRNAs. Various circRNAs are listed that sponge miRNAs under circadian control. Moreover, the intercellular spreading of information transmitted by miRNAs, circRNAs and lncRNAs via exosomes and ectosomes is addressed.