Dr. Melissa Conroy

Summary

Obesity is a global health problem affecting millions of adults and children worldwide. In Ireland, approximately 66% of adults and 25% of children are overweight or obese and are therefore at serious risk of developing obesity-associated diseases. Obesity induces organ and whole body chronic inflammation. It is the active infiltration of immune cells into expanding visceral adipose tissue (VAT) that causes this inflammation in obesity and studies have shown that T cells are predominantly responsible for this. VAT surrounds abdominal organs and its expansion is closely associated with obesity-related pathologies including many types of cancer and liver disease. Therefore, we propose that preventing T cells from infiltrating the VAT will prevent or reduce local and systemic inflammation and as a result the associated comorbidities. Proteins known as chemokines are responsible for guiding the migration of immune cells during normal immune responses and it is now well documented that chemokines mediate the natural cycling of T cells to the liver. However, previous murine studies have implicated dysregulated chemokine production in the recruitment of inflammatory cells to the VAT in obesity. Our recent work has revealed preferential movement of T cells to human VAT and liver and have identified two key chemokines guiding this movement; macrophage inflammatory protein 1α (MIP-1α) and interferon-inducible protein 10 (IP-10). Therefore, we propose that a therapeutic strategy specifically blocking MIP-1α- and IP-10-guided inflammatory T cell trafficking to the VAT and liver using novel chemokine receptor antagonists will prevent and reduce both local and systemic chronic inflammation in obesity. For the first time, this innovative study will validate a novel immunotherapeutic strategy targeting immune cell trafficking, which has significant potential to prevent and reduce the detrimental consequences of obesity-associated inflammation, as a major driver of carcinogenesis and liver disease, in the rapidly growing number of obese individuals worldwide.

Funding Agency

Irish Research Council

Programme

Government of Ireland Postdoctoral Fellowship

Project Type

Research