Boston, Mass. -- Researchers from Schepens Eye Research Institute of Massachusetts Eye and Ear have uncovered two factors responsible for the chronic, lifelong nature of autoimmune disorders, which tend to "flare up" intermittently in affected patients. These two factors are cell-signaling proteins called cytokines--specifically Interleukin-7 and -15 (IL-7 and IL-15)--that are secreted by cells of the immune system and help modulate memory Th17 cells, a subset of T cells which are known to contribute to autoimmune disorders. Until now, it was unclear how Th17 cells maintained memory; the study results show that IL-7 and IL-15 signal the Th17 cells to chronically reside in the body. These findings, published online in the Journal of Autoimmunity, may lead to the development of new therapies to address a variety of chronic autoimmune disorders.
"We wanted to know the precise factors that maintain memory in Th17 cells so that we can better understand what is causing chronic autoimmune disorders," said senior author Reza Dana, M.D., M.Sc., MPH, Director of the Cornea and Refractive Surgery Service at Mass. Eye and Ear and the Claes H. Dohlman Professor of Ophthalmology at Harvard Medical School. "By selectively targeting the production and expression of IL-7 and IL-15, we may be able to prevent the development of chronic autoimmune disorders."
Affecting up to 50 million Americans, autoimmune disorders develop when the body's immune system attacks its own healthy tissue. Many autoimmune disorders are chronic, and patients may experience "flare-ups," in which symptoms worsen temporarily and then enter a period of remission.
Previous research studies have linked Th17 cells to a variety of autoimmune disorders, including multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, and chronic inflammatory eye disorders such as uveitis and dry eye disease. When Th17 cells are activated, a subset of them become memory cells, causing them to reside in the body for long periods of time. These memory Th17 cells can become reactivated and cause flare-ups of the autoimmune condition. However, the underlying mechanisms that promote the maintenance of Th17 memory were previously unknown.
Using a mouse model for dry eye disease, an autoimmune condition affecting the surface of the eye, the study authors set out to determine what molecular factors are critical for the maintenance of Th17 memory. They identified IL-7 and -15 as playing a crucial role in the survival and homeostatic proliferation of memory Th17 cells, and when they neutralized IL-7 and IL-15, they saw a substantial reduction of memory Th17 cells.
While further studies are needed to determine ways to block these factors, the findings suggest that targeting IL-7 and IL-15 in order to remove the memory Th17 cells may be an effective treatment strategy for autoimmune diseases.
"In the case of dry eye disease, many of the treatments are showing limited efficacy in patients that do not have a highly inflamed eye," said Dr. Dana. "Targeting the chronic, immune nature of autoimmune diseases may be a better strategy for controlling these conditions."
Authors on the Journal of Autoimmunity report include Dr. Dana, Yihe Chen, M.D., Sunil K. Chauhan, Ph.D. and Xuhua Tan, M.D., Ph.D., of the Schepens Eye Research Institute of Massachusetts Eye and Ear and the Department of Ophthalmology at Harvard Medical School. This research was supported by National Institutes of Health grant R01EY20889. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
About Massachusetts Eye and Ear
Mass. Eye and Ear clinicians and scientists are driven by a mission to find cures for blindness, deafness and diseases of the head and neck. Now united with Schepens Eye Research Institute, Mass. Eye and Ear is the world's largest vision and hearing research center, developing new treatments and cures through discovery and innovation. Mass. Eye and Ear is a Harvard Medical School teaching hospital and trains future medical leaders in ophthalmology and otolaryngology, through residency as well as clinical and research fellowships. Internationally acclaimed since its founding in 1824, Mass. Eye and Ear employs full-time, board-certified physicians who offer high-quality and affordable specialty care that ranges from the routine to the very complex. In the 2016-2017 "Best Hospitals Survey," U.S. News & World Report ranked Mass. Eye and Ear #1 in the nation for ear, nose and throat care and #1 in the Northeast for eye care. For more information about life-changing care and research, or to learn how you can help, please visit MassEyeAndEar.org.
About the Harvard Medical School Department of Ophthalmology
The Harvard Medical School (HMS) Department of Ophthalmology (eye.hms.harvard.edu) is one of the leading and largest academic departments of ophthalmology in the nation. More than 350 full-time faculty and trainees work at nine HMS affiliate institutions, including Massachusetts Eye and Ear, Massachusetts General Hospital, Brigham and Women's Hospital, Boston Children's Hospital, Beth Israel Deaconess Medical Center, Joslin Diabetes Center/Beetham Eye Institute, Veterans Affairs Boston Healthcare System, VA Maine Healthcare System, and Cambridge Health Alliance. Formally established in 1871, the department has been built upon a strong and rich foundation in medical education, research, and clinical care. Through the years, faculty and alumni have profoundly influenced ophthalmic science, medicine, and literature--helping to transform the field of ophthalmology from a branch of surgery into an independent medical specialty at the forefront of science.
Journal of Autoimmunity