The way our body responds to invading microorganisms is a tightly regulated process. When challenged with a pathogen, our immune system must eliminate this danger but also self-regulate to ensure homeostasis is maintained. If this system falls out of balance, uncontrolled inflammation occurs and the immune system damages human tissue. This underpins the progression of chronic inflammatory diseases, such as rheumatoid arthritis as well as the inflammation associated with type-II diabetes, allergic disease, and some cancers. The immense burden of these conditions on individual patients and healthcare systems alike has pushed immunological research towards the understanding of these disease states, in the hope of finding suitable markers for disease activity and new treatments. This involves the study of the entire disease pathway, starting with clinical observations and progressing to genome-wide analyses of patients.
Dr. Esperanza Perucha and her lab (the SpLAB) at King’s College London, investigates the precise cellular and molecular mechanisms of the immune cells which mediate inflammation, and the important switch these cells must make (from pro-inflammatory to anti-inflammatory) to protect the body from states of chronic inflammation. Using in vitro human culture systems, SpLAB has uncovered important metabolic changes in certain immune cells which drive the switch from a pro-inflammatory to an anti-inflammatory state. Research which links immunology and metabolism is termed ‘immunometabolism’, a field which has exploded in the last ten years.
The SpLAB has identified cholesterol metabolism as critical for driving the switch from pro-inflammatory to anti-inflammatory in a type of immune cell called CD4, a highly adaptive cell belonging to the T-lymphocyte family. Cholesterol metabolism in these cells is able to regulate the expression of important genes involved in immune regulation, especially interleukin 10 (IL-10). IL-10 is crucial for balancing the immune response and protecting the host from tissue damage, and by extension chronic inflammation. Figuring out how and why reduced IL-10 is produced by these CD4 cells, and the role of cholesterol metabolism in this process, has huge potential for furthering our understanding of why chronic inflammation occurs and causes disease states in some individuals. If the role of cholesterol metabolism is significant, future treatments may focus on targeting this metabolic pathway specifically to mediate inflammation
Dr Perucha is interested in better understanding the importance of cholesterol metabolism at the molecular, cellular, and organismal level; this is hindered by the lack of validated and simplified methods to measure cholesterol metabolism. Alongside investigating the role of cholesterol metabolism in this way, Dr Perucha is also looking to establish a methodology for the quantification of cholesterol metabolism. Not only will this serve to fulfil her aims, a standardised methodology will reaffirm the importance of cholesterol metabolism and support a global chain of scientists interested in better understanding it’s impact in health and disease. A growing knowledge base serves to benefit the patient directly; greater acuity of how this metabolic pathway can be modulated could translate into cholesterol-targeted therapeutics. This may result in better treatments for chronic inflammatory diseases, cancer, allergy conditions and beyond.
This research would form a foundation for future immunometabolism studies which have shown great promise in helping understand the complex mechanisms which underlie chronic inflammatory diseases and cancer. The field of immunometabolism demands a global view of human health, given that it interlinks with other exciting research areas such as diet and the microbiome. The synergy of these research fields holds great promise in the novel treatment of chronic inflammatory diseases, and for re-evaluating the relationship between the external environment and our health and lifestyle.
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