| First Author | Wang Q | Year | 2019 |
| Journal | Sci Immunol | Volume | 4 |
| Issue | 40 | PubMed ID | 31586012 |
| Mgi Jnum | J:293684 | Mgi Id | MGI:6453578 |
| Doi | 10.1126/sciimmunol.aay7501 | Citation | Wang Q, et al. (2019) Circadian rhythm-dependent and circadian rhythm-independent impacts of the molecular clock on type 3 innate lymphoid cells. Sci Immunol 4(40) |
| abstractText | Many gut functions are attuned to circadian rhythm. Intestinal group 3 innate lymphoid cells (ILC3s) include NKp46(+) and NKp46(-) subsets, which are RORgammat dependent and provide mucosal defense through secretion of interleukin-22 (IL-22) and IL-17. Because ILC3s highly express some key circadian clock genes, we investigated whether ILC3s are also attuned to circadian rhythm. We noted circadian oscillations in the expression of clock and cytokine genes, such as REV-ERBalpha, IL-22, and IL-17, whereas acute disruption of the circadian rhythm affected cytokine secretion by ILC3s. Because of prominent and rhythmic expression of REV-ERBalpha in ILC3s, we also investigated the impact of constitutive deletion of REV-ERBalpha, which has been previously shown to inhibit the expression of a RORgammat repressor, NFIL3, while also directly antagonizing DNA binding of RORgammat. Development of the NKp46(+) ILC3 subset was markedly impaired, with reduced cell numbers, RORgammat expression, and IL-22 production in REV-ERBalpha-deficient mice. The NKp46(-) ILC3 subsets developed normally, potentially due to compensatory expression of other clock genes, but IL-17 secretion paradoxically increased, probably because RORgammat was not antagonized by REV-ERBalpha. We conclude that ILC3s are attuned to circadian rhythm, but clock regulator REV-ERBalpha also has circadian-independent impacts on ILC3 development and functions due to its roles in the regulation of RORgammat. |
