Regular daily changes between light and dark has enormous impacts on behavior and physiology of humans and many other mammals (also known as circadian rhythm). Disturbance of normal circadian rhythm in humans by shifted work, sleep disorders or frequent inter-continental flights is causally associated with obesity, cardiovascular diseases and intestinal disorders such as irritable bowel syndrome or inflammatory bowel disease. In a new study published on Oct. 4th, 2019 in Science Immunology and highlighted by the journal cover image, researchers from Weill Cornell Medicine have identified that the homeostasis of group 3 innate lymphoid cells (ILC3s), one of the key immune cell populations regulating intestinal immunity and barrier function, critically requires circadian rhythm.
The study was led by Dr. Gregory Sonnenberg, an associate professor of microbiology and immunology in medicine in the Division of Gastroenterology and Hepatology and a member of the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine, and Dr. Fei Teng, a postdoctoral researcher in the Sonnenberg Lab. The researchers found that intestinal ILC3s in mice exhibit diurnal oscillations in genes involved in both circadian clock and classical ILC3 effector functions in response to light signals. By genetic ablation of this pathway, they also found circadian regulation is essential for survival and appropriate cytokine production of ILC3s in the presence of intestinal commensal bacteria. Lastly, the researchers identified ILC3s isolated from the inflamed intestine of patients with inflammatory bowel disease exhibited substantial alterations in expression of several circadian-related genes. This study has uncovered a previously under-appreciated role of circadian rhythm on the homeostasis of intestinal ILC3s and suggested that this pathway may serve as a novel target to boost or restore normal ILC3 responses in the context of intestinal inflammation.
This work is in collaboration with Dr. Manish A. Shah (NewYork-Presbyterian Hospital) and Dr. Gérard Eberl (Institut Pasteur, France) and was supported by the NIH (R01AI143842, R01AI123368, R01AI145989, and U01AI095608), the NIAID Mucosal Immunology Studies Team (MIST), the Crohn’s and Colitis Foundation of America, the Searle Scholars Program, the American Asthma Foundation Scholar Award, Pilot Project Funding from the Center for Advanced Digestive Care (CADC), an Investigators in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund, a Wade F.B. Thompson/Cancer Research Institute CLIP Investigator grant, the Cancer Research Institute Lloyd J. Old STAR Program, the Meyer Cancer Center Collaborative Research Initiative, and the Jill Roberts Institute (JRI) for Research in IBD.