The Role of the Immune System in COPD and Lupus
The underlying mechanisms of the immune system may lead to new treatments for COPD and lupus.
Three recent studies discovered what role the immune system plays in chronic obstructive pulmonary disease (COPD) and systemic lupus erythematosus (SLE) and the underlying mechanisms of the diseases.
The studies, published in Nature Immunology, cover the immune system and COPD, the immune system and ILCs, and the immune system and lupus.
“The novel findings presented in Nature Immunology challenge the status quo, further our understanding of COPD and lupus, and most importantly, will help increase the scientific community's understanding of the immune system,” said Bahija Jallal, executive vice president of MedImmune. “Hopefully this will bring us one step closer to developing more effective treatments for patients in the future.”
Immune System and COPD
During the study, researchers examined how the tissue-protective Group 2 Innate Lymphoid Cells (ILC2s) are able to change once exposed to stimuli, such as cigarette smoke or an infection. Prior research suggested that smoking alters the activity of the immune system in the lungs, leaving noticeable side effects that skew ILC2s activity.
The results of the study showed that ILC2s in the lungs of mice both changed and gained physical characteristics similar to inflammatory ILC1s when exposed to cigarette smoke or infection and in the presence of interleukin (IL)-12 and IL-18, two key inflammatory signals.
The study findings suggest that changes in circulating ILC’s could predict which patients are at risk, allowing for the possibility to treat COPD exacerbations by manipulating ILC1s back into ILC2s.
“Our research shows how versatile and adaptive the immune system can be,” said MedImmune principal scientist Alison Humbles, PhD. “By simply converting one into another, the immune system can switch between ILC2-associated tissue protection and ILC1-driven inflammation. This research is a significant step toward understanding the pathogenesis of chronic diseases like COPD and can guide future therapeutic strategies.”
Immune System and ILCs
A second study examined how the switch between ILC1s and ILC2s is regulated in human cells. The study found that the IL-1 cytokine gives signals that cause a significant increase in ILC2s that subsequently mature into fully functional cells.
IL-1 is also able to stimulate changes in ILC2s that give them the ability to be changed into ILC1s when being simultaneously exposed to IL-12. Additionally, researchers highlighted that IL-1 is an upstream regulator of epithelial cell-derived cytokines (IL-33, IL-25, and TSLP), which are primary activators of ILC2s.
The findings suggest that there could be another cellular pathway that is able to regulate ILC2s function besides epithelial cells.
“This research opens an entirely new line of investigation into ILC2s,” said researcher Yoichiro Ohne, PhD. “We now know more about ILC2s, how their activity and plasticity are regulated and key triggers, which gives us multiple options in targeting their activity in situations where we think they're driving disease. This is an important step in the search for potential therapeutics that can restrain inflammation cycles that are excessive and damaging, such as in COPD.”
Immune System and Lupus (SLE)
The antibody IgE, commonly known to target allergens and produce a histamine response in people with allergies, was found to also malfunction and target the body’s own DNA, a third study found. This malfunction and targeting of DNA triggers a pathogenic secretion of IFN-a (immune system activator molecule), which leads to lupus-associated tissue damage.
During the study, 54.4% of lupus patients had DNA-specific IgE that contributed to autoimmunity by triggering the secretion of IFN-a. Additionally, an association between the concentration of DNA-specific IgE in the blood and the severity of the disease was found.
The findings suggest, that IgE could be useful for evaluating the effectiveness of lupus treatments and could also be potentially used as a therapeutic target.
“This research has led to a groundbreaking discovery that IgE leads a double life as a trigger of allergy symptoms and a self-destructive agent in SLE,” said Miguel Sanjuan, PhD, Researcher, MedImmune. “These findings could have tremendous implications for the lupus community. In addition to the potential of targeting IgE in lupus patients, these findings show the scientific research community that there is a new realm of previously unknown activity of IgE that unleashes its pathogenic potential beyond orchestrating allergy symptoms, which may also be responsible for other autoimmune conditions.”