MedImmune, the global biologics research and development arm of AstraZeneca, today announced that it has achieved a significant scientific milestone by publishing three manuscripts in Nature Immunology that advance the understanding of the immune system and highlight underlying mechanisms in two little-understood disease areas – chronic obstructive pulmonary disease (COPD) and systemic lupus erythematosus (SLE). These include:
- The Immune System and COPD: “Inflammatory triggers associated with COPD exacerbations orchestrate ILC2 plasticity in the lung”
Researchers found that tissue-protective Group 2 Innate Lymphoid Cells (ILC2s) in the lungs of mice changed and acquired physical characteristics similar to inflammatory ILC1s when exposed to cigarette smoke and/or infection in the presence of two key inflammatory signals: Interleukin (IL)-12 and IL-18.
- The Immune System and ILCs: “IL-1 is a critical regulator of Group 2 Innate Lymphoid Cell function and plasticity”
- Researchers found that the IL-1 cytokine provides signals that cause ILC2s to significantly increase in number and mature into fully functional cells.
- The Immune System and lupus: “Self-reactive IgE exacerbates interferon responses associated with autoimmunity”
- Researchers found that 54.4 percent of lupus patients studied had DNA-specific IgE, and that this self-reacting antibody contributes to autoimmunity by triggering the secretion of IFN-a, a central inflammatory mediator of lupus pathogenesis.
“At MedImmune, we put great emphasis on science and understanding the pathophysiology of disease,” said Bahija Jallal, Executive Vice President, MedImmune. “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. Hopefully this will bring us one step closer to developing more effective treatments for patients in the future.”
The Immune System and COPD
Published today, “Inflammatory triggers associated with COPD exacerbations orchestrate ILC2 plasticity in the lung,” researchers studied the way that a type of immune cell known as ILC2 changes when exposed to stimuli such as cigarette smoke and/or infection. Previous research had indicated that smoking alters the immune system’s activity in the lungs, and has noticeable effects that seem to skew the activity of ILC2s.
- Researchers found that tissue-protective ILC2s in the lungs of mice changed and acquired physical characteristics similar to inflammatory ILC1s when exposed to cigarette smoke and/or infection in the presence of two key inflammatory signals: IL-12 and IL-18.
- The same activity may be occurring in COPD, as those patients with a higher ratio of circulating ILC1s in blood had more severe disease and a higher number of exacerbations in the year prior.
- The findings suggest that changes in circulating ILC populations may predict patients at risk and that it may be possible to treat COPD exacerbations by manipulating the switch of ILC1s back into ILC2s.
“Our research shows how versatile and adaptive the immune system can be,” said Alison Humbles, Ph.D., Principal Scientist, MedImmune. “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.”