Ling Pei Ho: Immune responses in lung disease - Sarcoidosis

Q: Why study immune responses in lungs?

Ling-Pei Ho: Most people understand the immune system as a collection of tissues and cells that help the body defend itself against infection - but is does more than that. The immune system has to be able to tolerate non-dangerous microbes, particularly in an organ like the lung where it is exposed to the environment every minute of the day. It needs to recognise what is and what is not harmful. It also needs to be able to regulate itself.  If any of these functions fail, then disease can ensue; one of these is sarcoidosis.  

Sarcoidosis is an immune disorder which can affect any organ in the body but primarily affects the lungs. For most patients the collection of symptoms is relatively mild, such as a cough, but for about 40% of patients it can be quite severe. Patients can become breathless due to excessive immune response (in the form of granuloma formation) or scarring (fibrosis). The condition can last for many years and in the worst affected patients this can lead to respiratory failure.

Q: What causes sarcoidosis?

LPH: The exact cause of sarcoidosis is unknown but we do know it is the result of an exaggerated immune response to an unknown environmental trigger. In Oxford we are more interested in defining the problems in the immune response rather than the triggers. For example, we have found that a group of powerful immune cells called the natural killer T cells are absent in a lot of patients with sarcoidosis. This group of immune cells controls the immune system, and loss of these cells could be a cause for excessive immune activity.

Q: What are the most important lines of research that have developed in the last 5-10 years?

LPH: The discovery from genome wide association studies that genes involved in regulating the immune system supports the idea that inability to regulate the immune response is one of the key mechanisms of this disease.

Q: Why does your line of research matter and why should we put money in to it?

LPH: Understanding the exact pathways causing the disease, or the cells that are involved, helps us find out which molecules or cells we can target for new therapies for this condition, particularly for those with lung scarring (fibrotic sarcoidosis). There are few new medicines available for sarcoidosis, and in fact the last 50 years we have not had a single medicine made specifically for sarcoidosis.

Q: How does your research fit into translational medicine within the Department?

LPH: We have shown that loss of natural killer T cells in sarcoidosis results in abnormal monocyte and T cell responses. We are now examining the causes of fibrotic sarcoidosis. These studies will provide a basis for new, or repositioning of current, drugs to the more severe end of the disease.