Discovery of elusive lymph macrophages' life cycle may shed light on autoimmune diseases.
Australian researchers recently announced that they had made a fundamental discovery about what happens in lymph nodes, shedding light on the causes of immune-related diseases such as lupus.
The results of the experimental study were recently published in the journal Cell, and the scientists at the Garvan Institute of Medical Research stated that they tracked the cell's lifecycle and function, which has implications for the understanding of autoimmune disorders.
According to various estimates, approximately 4% of the global population suffers from one of over 80 different autoimmune diseases, the most common of which are type 1 diabetes, multiple sclerosis, rheumatoid arthritis, lupus, Crohn's disease, psoriasis, and scleroderma.
“In living organisms, death happens all the time, and if you do not clean up, the contents of the dead cells can trigger autoimmune diseases,” lead author Professor Tri Phan, Head of the Intravital Microscopy and Gene Expression (IMAGE) Lab and Co-Lead of the Precision Immunology Program at Garvan, said.
Though macrophages in many parts of the body are responsible for clearing foreign material such as bacteria and viruses, the researchers discovered that these tingible body macrophages, found inside lymph nodes, specialise in cleaning up the waste of the body's immune system, called B cells that proliferate when the body fights infection.
During an immune response, the lymph nodes produce numerous B cells, which are tested for their ability to neutralise the infection. B cells that fail the test are destined to perish, but on their way out they can cause the body to attack itself.
The contents of these cells, especially those in the central nucleus, are inflammatory in nature and can inadvertently activate some B cells to make antibodies against that waste, leading to autoimmunity, the researchers added.
Using state-of-the-art intravital imaging techniques to observe how the macrophages form within the lymph nodes and how they behave in real time, the scientists found that, unlike other immune cells, tingible body macrophages do not chase their targets but disperse evenly and lie in wait. When a dead or dying B cell comes close, the macrophage reaches out and ingests them.
“We know so very little about tingible body macrophages because it was not possible until now, with next-generation two-photon microscopes, to get inside the microstructures inside the lymph nodes of a living animal and watch the cells in action in real-time,” Professor Phan said.
Pointing out that this research will help the scientific community to understand the causes of autoimmune conditions like lupus, co-author Wunna Kyaw said, “Understanding why somebody gets the disease in the first place and why it keeps coming back is an important step towards future treatments for these diseases.”
The study has so far examined what happens with the macrophages in healthy animal models and the researchers will now have to expand the experiment to an autoimmune model to see if they can rescue the failing system and prevent autoimmunity at its root cause.
