The Hospital for Special Surgery (HSS) in New York City has discovered a molecule in the lymphatic system that could possibly be a factor in autoimmune disease. Theresa Lu, MD, PhD, led the charge at the HSS Research Institute and, along with colleagues, commenced a research initiative to improve our understanding of the inner workings of the immune system.
A recent study titled “Lymph node stromal CCL2 limits antibody responses” was recently published online in the Journal of Science Immunology.
Why is this research finding important?
Well diseases such as lupus, rheumatoid arthritis and scleroderma are examples of what can become horrific autoimmune disease. In fact, people can lose their lives due to these diseases. Their health degrades because their immune system function is out of whack and doesn’t protect their own bodies against disease and infection.
If scientists can better understand the underlying mechanisms that cause autoimmune and inflammatory conditions, they can develop ways to correct the immune system flaws that lead to disease and unfortunately at times death and the loss of loved ones.
What was the angle that the HSS researchers took in this study?
Dr. Lu and team focused on the lymphoid tissues, which actually house immune cells and sites of immune cell activation. As it turns out, lymphoid tissues (e.g. tonsils, spleen, lymph nodes, etc.) contain structural elements, such as fibroblasts and blood vessels. For a long time it was thought that these structural elements served as an infrastructure for the immune cells. However, recent advances in the field evidence that they actually shape immune cell responses; moreover multiple populations of fibroblasts have different functions.
What were some of Dr. Lu and HHS team findings?
She reported that actually that one “fibroblast population expressed a molecule called CCL2 in the area of the antibody—secreting immune cells, called plasma cells.” They centered their studies on the CCL2-expressing fibroblasts to see if they regulate plasma cell function,” Lu noted in the recent press release. Upon further analysis, they discovered that “CCL2 limits the magnitude of plasma cell responses by acting as an intermediary cell to reduce plasma cell survival.” The HSS researchers were taken aback as they knew that CCL2 can promote inflammation and yet they found this activity where it was limiting immune responses. Lu noted, “This underscores the multiple functions that any molecule can have in different contexts.”
Why is this finding relevant?
Well, the HHS team wrote that the findings could have implications for greater understanding of autoimmune diseases, reported Dr. Lu. For example, plasma cells in autoimmune disease generate autoantibodies that then help deposit and cause inflammation in organs such as the kidney and skin.
So Lu continued, “By understanding that plasma cells can be controlled by this subset of fibroblasts, we can study these fibroblasts to see if they are perhaps not working properly in autoimmune and inflammatory diseases. We can then search for a way to correct the malfunction, so they are less likely to cause disease.”
How can learning more about manipulating fibroblasts help progress research?
Our immune systems are absolutely vital to the healthy functioning of our bodies and can act in comparable ways in various different settings; hence, learning about manipulating fibroblasts can also support the research sector in improving their comprehension of how to treat related process—from “healing after a musculoskeletal injury, fighting cancer and fighting infections.” So moving forward researchers, for example in the context of the COVID-19 crisis, can examine medications by segment (e.g. adults or children) and by different autoimmune disease type (e.g. lupus or RHS) to better learn how the manipulation of fibroblasts may impact one group over another.
Who is the study team?
In addition to Dr. Theresa Lu, MD, HSS colleagues include Dragos Dasoveanu, PhD, Will Shipman, PhD, Susan Chyou, BA and Varsha Kuma, PhD. Other scientists from research centers in New York, Switzerland and Australia collaborated on the study.
Hospital for Special Surgery Background
HSS is the world’s leading academic medical center focused on musculoskeletal health. At its core is Hospital for Special Surgery, nationally ranked No. 1 in orthopedics (for the tenth consecutive year), No. 3 in rheumatology by U.S. News & World Report (2019-2020), and named a leader in pediatric orthopedics by U.S. News & World Report “Best Children’s Hospitals” list (2019-2020). Founded in 1863, the Hospital has one of the lowest infection rates in the country and was the first in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center four consecutive times. The global standard total knee replacement was developed at HSS in 1969. An affiliate of Weill Cornell Medical College, HSS has a main campus in New York City and facilities in New Jersey, Connecticut and in the Long Island and Westchester County regions of New York State. In addition, HSS will be opening a new facility in Florida in early 2020. In 2018, HSS provided care to 139,000 patients and performed more than 32,000 surgical procedures, and people from all 50 U.S. states and 80 countries travelled to receive care at HSS. There were more than 37,000 pediatric visits to the HSS Lerner Children’s Pavilion for treatment by a team of interdisciplinary experts. In addition to patient care, HSS leads the field in research, innovation and education. The HSS Research Institute comprises 20 laboratories and 300 staff members focused on leading the advancement of musculoskeletal health through prevention of degeneration, tissue repair and tissue regeneration. The HSS Global Innovation Institute was formed in 2016 to realize the potential of new drugs, therapeutics and devices. The HSS Education Institute is the world’s leading provider of education on musculoskeletal health, with its online learning platform offering more than 600 courses to more than 21,000 medical professional members worldwide. Through HSS Global Ventures, the institution is collaborating with medical centers and other organizations to advance the quality and value of musculoskeletal care and to make world-class HSS care more widely accessible nationally and internationally.