Grant: Travel Awards - Institute Community Support

Innate sensors are tightly regulated to allow early detection of low levels of microbial molecules while avoiding recognition of self molecules. Understanding the fine-tuning of innate sensor expression in tissues is important to understand when and where cells sense pathogencs or contribute to autoinflammatory disorders. Mutations that inactivate innate sensors can predispose people to infectious disease, while overactive innate sensors can cause aberrant inflammation and autoimmunity. In my postdoc, I used intestinal organoids as a 3D culture model to mimic human intestinal epithelium. I found that TLR3 is a critical innate sensor in the intestinal epithelium to sense enteroviruses. I found that enterocytes upregulate TLR3 and become more responsive to virus as they migrate from stem-cell containing intestinal crypts toward terminally differentiated intestinal villi. I am now using 3D human skin cultures and transcriptome analyses to investigate patterns of innate sensor expression in the context of healthy and psoriatic skin. By understanding how healthy and lesional skin responds to innate immune stimuli we will gain a better understanding of environmental drivers of psoriasis and psoriatic arthritis.