GAITHERSBURG, Md.—April 25 brought an announcement by MedImmune, the global biologics research and development arm of AstraZeneca, that it has achieved what it sees as “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).

 

“At MedImmune, we put great emphasis on science and understanding the pathophysiology of disease,” said Bahija Jallal, executive vice president of 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.”

 

Taking it all in brief, two of the studies were COPD-related primarily: “Inflammatory triggers associated with COPD exacerbations orchestrate ILC2 plasticity in the lung” and “IL-1 is a critical regulator of Group 2 Innate Lymphoid Cell function and plasticity.” In the first, 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. In the second study, the findings were that the IL-1 cytokine provides signals that cause ILC2s to significantly increase in number and mature into fully functional cells.

 

Meanwhile, for the third study, which was SLE-focused and titled “Self-reactive IgE exacerbates interferon responses associated with autoimmunity,” the 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.

 

Now, on to more detail:

 

 

In “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. Study highlights:

“Our research shows how versatile and adaptive the immune system can be,” said Dr. Alison Humbles, 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.”

 

 

In “IL-1 is a critical regulator of Group 2 Innate Lymphoid Cell function and plasticity,” researchers provided further mechanistic insights into how the switch between ILC1s and ILC2s is regulated in human cells. This study shows that the adaptability (or “plasticity”) of ILC2s is mediated by a kind of master switch known as IL-1. Study highlights:

“This research opens an entirely new line of investigation into ILC2s,” said Dr. Yoichiro Ohne, a MedImmune scientist. “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.”

 

 

In “Self-reactive IgE exacerbates interferon responses associated with autoimmunity,” researchers showed that IgE—an antibody most commonly known to target allergens and produce the histamine response in people with allergies—can also malfunction and target the body’s own DNA. This triggers pathogenic secretion of an immune system activator molecule called IFN-a, which ultimately causes the tissue damage associated with lupus. Study highlights:

“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. These findings could have tremendous implications for the lupus community,” said Dr.Miguel Sanjuan, Ph.D., a researcher at MedImmune. “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.”