Researchers discovered that a receptor vital to iron processing in the lungs is much less common in patients with idiopathic pulmonary fibrosis (IPF).
IPF is a chronic lung disease where the build-up of scar tissue in the lungs makes it harder to breathe. About 6,000 people are diagnosed with IPF every year in the UK. A study led by the National Heart and Lung Institute has found that lungs of IPF patients have a reduced ability to process iron due to a missing receptor. This iron may come from our diet or it can be inhaled, for example in air pollution. An IPF patient’s condition gets worse over time due to a decline in lung function, and there are limited treatments available to help reduce the rate of decline. However currently there is nothing available to halt or reverse the scarring of the lungs. New research led by Dr Adam Byrne, Professor Clare Lloyd and Professor Toby Maher has shown that patients with fewer of the working iron receptors are likely to decline quicker than those with more. This suggests further work needs to be done to look at how we can use this new discovery to develop treatments.
“Anything we can do to make strides towards new therapies and understanding this disease is extremely important” Dr Adam Byrne Joint-lead author
During IPF there is a population of immune cells in the lungs that have an impaired ability to process iron which is an important defence mechanism against pollutants and invading bacteria. The numbers of these impaired cells are increased in IPF patients with more severe forms of the disease. As a result, the numbers of these defective cells can be used to predict a patient’s survival. The immune cells effected are the airway macrophages which play an important role in the defence of our airways, removing a variety of particles that enter our lungs that could cause our body harm, including iron. Researchers found that patients at the Royal Brompton Hospital with IPF had a higher number of airway macrophages completely missing the receptor CD71 (used to process iron) than in those without IPF. Therefore these patients are less effective at processing iron.
The iron obtained through your diet is generally good for you, but too much iron, present in for instance pollution, can be bad, particularly in your lungs. Having identified this reduced ability to process iron in IPF patients we can consider tackling it in two ways. Either the excess iron can be mopped up with drugs, or we can try to help fix the macrophages. More work will need to be done to understand how we can help macrophages to process iron better, which would probably involve targeting the receptor CD71. Of course the more we can do to reduce pollution the better it will be for IPF patients ill-equipped to deal with iron. This makes clean air policies and environmental work to reduce emissions particularly relevant to those with lung disease.
One of the knock-on effects from the faulty CD71 receptor is that IPF patients have a higher number of bacteria in their lungs. Bacteria need iron as a nutrient, but the macrophages are meant to out compete bacteria for iron, getting there first so bacteria cannot use it. The defective macrophages found in IPF lungs may allow bacteria to flourish.
The team chose to look at CD71 because they had noticed that when macrophages in the lung get activated, they change this receptor, so decided to take a closer look. However, they were surprised to find such a large population of these macrophages in IPF patients that did not express the receptor. The next step will be to figure out what is happening in the entire iron pathway - what happens next once the iron is in our body? Iron is linked to the metabolism of cells, so the researchers plan to compare the metabolism of macrophages that do and don’t have the receptor. It could be that the metabolism is tied up with the poor outcome for patients, perhaps the macrophages can’t function as they are exhausted and therefore can’t process iron.
Read the full publication on “The Transferrin Receptor CD71 Delineates Functionally Distinct Airway Macrophage Subsets during Idiopathic Pulmonary Fibrosis” in the American Journal of Respiratory and Critical Care Medicine.
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