PTPN2 and TiO2 in the pathogenesis of Inflammatory Bowel Disease
Javier Conde Aranda
© Javier Conde Aranda
Aim of the research
Titanium dioxide (TiO2) may play a pivotal role in the onset and perpetuation of chronic intestinal inflammation. These effects may be genetically triggered, and variations in IBD risk genes, such as PTPN2, may contribute critically to the detrimental effect of TiO2 in vivo. For these reasons, we will study the combined effects of the presence of disease-associated genetic PTPN2 variations and TiO2 microparticles on the development of chronic intestinal inflammation and on inflammasome activity, as well as the subsequent consequences for the host immune system, in particular innate immune responses. The study will demonstrate the relevance of TiO2 in the pathogenesis of intestinal inflammation in vivo. To address the aforementioned aims, we will:
1. Analyse whether PTPN2-mediated inflammasome activation can control TiO2-induced intestinal inflammation.
2. Demonstrate whether the presence of the disease-associated PTPN2 variant affects NLRP3 inflammasome activation and intestinal inflammatory responses to TiO2 in IBD patients.