IL-22 IN OBESITY AND OBESITY-ASSOCIATED CANCER

Washington University, Saint Louis MO

Investigators

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Abstract

DESCRIPTION (provided by applicant): Obesity, which is an epidemic in the United States, increases the risk of developing cancer. Recently, it has been determined that obesity is associated with chronic low-grade inflammation that requires elements of the immune system. In our preliminary data we find that obese people have a Thelper (TH)22/TH17 signature in blood and adipose tissue, most likely linked to the ongoing inflammation. Interleukin-22 (IL-22) has important proliferative and wound-healing properties on epithelial and stromal cells necessary to maintain homeostasis at mucosal sites. However, we postulate that persistent IL-22 secretion may drive uncontrolled epithelial proliferation and tumor development. IL-22 in adaptive and innate cells is under the control of a transcription factor known as Aryl Hydrocarbon Receptor (AHR). AHR signaling is activated by endogenous ligands but also by diet-associated compounds and environmental products. We plan to test the hypothesis that AHR signaling may favor cancer development in obesity by potentiating IL-22 production. These studies may open new avenues of therapeutic intervention through diet to prevent cancer associated to obesity.