The Department of Biochemistry's weekly BCH 252 seminar series is presented this week by
Vinicius Canale, Ph.D. candidate, BCMB Graduate Program, University of California Riverside
Seminar Title: "PTPN2 is a Critical Regulator of Paneth Cell Viability and Homeostasis in Mice"
Abstract: Single nucleotide polymorphisms (SNPs) found in the protein tyrosine phosphatase non-receptor Type 2 (PTPN2) gene locus are associated with increased risk of Inflammatory Bowel Disease (IBD). PTPN2 encodes T Cell Protein Tyrosine Phosphatase (TCPTP), a negative regulator of intracellular signaling pathways including JAK-STAT. The intestinal barrier comprises three layers of protection: the mucus layer, the intestinal epithelial cell (IEC) lining and the underlying immune cells. A healthy IEC layer functions as a selectively permeable barrier at the host-microbiome interface, and is essential for generating ion solute concentration gradients, absorption of nutrients, sampling of bacterial antigens, restricting entry of pathogens and toxins, modulating the microbial intestinal flora by secreting anti-microbial components and mediating communication with the immune system. These functions are accomplished by a set of specialized and highly differentiated IECs subtypes, each of them strategically located in the crypt-villus axis of the small intestine. Normally, IEC subtypes are functionally altered in IBD although such impairments are dependent on IBD entity (Crohn’s disease vs. ulcerative colitis), genetic susceptibility and site of disease activity. In this study we aimed to identify how Ptpn2-loss-of-function affects ileal IEC subtypes and their function in vivo. We observed that constitutive Ptpn2-deficiency alters the expression of several IECs markers in mice. Notably, the number of PCs were dramatically reduced negatively affecting the production of antimicrobial peptides (AMPs) that directly modulates the intestinal microbiota, indicating a newly identified mechanism by which Ptpn2-loss of function might increase susceptibility to infection, contribute to intestinal dysbiosis and disease onset.
Dr. Li Fan, email@example.com