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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Circadian rhythm-dependent and circadian rhythm-independent impacts of the molecular clock on type 3 innate lymphoid cells

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Wang, Qianli [1] ; Robinette, Michelle L. [1, 2] ; Billon, Cyrielle [3, 4] ; Collins, Patrick L. [5] ; Bando, Jennifer K. [1] ; Fachi, Jose Luis [1, 6] ; Secca, Cristiane [1] ; Porter, Sofia I. [5] ; Saini, Ankita [5] ; Gilfillan, Susan [1] ; Solt, Laura A. [7] ; Musiek, Erik S. [8] ; Oltz, Eugene M. [5] ; Burris, Thomas P. [3, 4] ; Colonna, Marco [1]
Total Authors: 15
[1] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 - USA
[2] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 - USA
[3] Washington Univ, Sch Med, Ctr Pharmacol Clin Appl Dermatol, Ctr Clin Pharmacol, St Louis, MO 63110 - USA
[4] St Louis Coll Pharm, St Louis, MO 63110 - USA
[5] Ohio State Univ, Coll Med, Dept Microbial Infect & Immun, Columbus, OH 43210 - USA
[6] Univ Estadual Campinas, Inst Biol, Dept Genet Evolut Microbiol & Immunol, Lab Immunoinflammat, BR-13083862 Campinas, SP - Brazil
[7] Scripps Res Inst, Dept Immunol & Microbiol, Jupiter, FL 33458 - USA
[8] Washington Univ, Sch Med, Dept Neurol, Hope Ctr Neurol Disorders, St Louis, MO 63110 - USA
Total Affiliations: 8
Document type: Journal article
Source: SCIENCE IMMUNOLOGY; v. 4, n. 40 OCT 2019.
Web of Science Citations: 1

Many gut functions are attuned to circadian rhythm. Intestinal group 3 innate lymphoid cells (ILC3s) include NKp46(+) and NKp46(-) subsets, which are ROR gamma t 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-ERB alpha, 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-ERB alpha in ILC3s, we also investigated the impact of constitutive deletion of REV-ERB alpha, which has been previously shown to inhibit the expression of a ROR gamma t repressor, NFIL3, while also directly antagonizing DNA binding of ROR gamma t. Development of the NKp46(+) ILC3 subset was markedly impaired, with reduced cell numbers, ROR gamma t expression, and IL-22 production in REV-ERB alpha-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 ROR gamma t was not antagonized by REV-ERB alpha. We conclude that ILC3s are attuned to circadian rhythm, but clock regulator REV-ERB alpha also has circadian-independent impacts on ILC3 development and functions due to its roles in the regulation of ROR gamma t. (AU)

FAPESP's process: 18/10165-0 - Role of microbiota-derived metabolites, the short-chain fatty acids, on innate lymphoid cells
Grantee:José Luís Fachi
Support type: Scholarships abroad - Research Internship - Doctorate