PTPN2 activation as a novel therapeutic target for the treatment of IBD

Inflammatory bowel diseases (IBD) are idiopathic, chronic inflammatory disorders of the gastrointestinal tract, classified into two major types: Crohn’s disease (CD) and ulcerative colitis (UC). A variety of environmental factors, as well as presence of genetic variants, dysregulated immune responses and changes in the intestinal microbiota have been associated with the development of IBD, however its aetiology still remains to be not fully understood. Genome wide association studies (GWAS) identified variants in the gene locus encoding for protein tyrosine phosphatase non-receptor type 2 (PTPN2) as an IBD risk genes. It is known that PTPN2 regulates intestinal epithelial barrier function, as well as immune cell functions in vitro and in vivo. Presence of PTPN2 variants in IBD patients results in dysfunctional PTPN2, promoting a more severe disease course, but at the same time a better response to anti-TNF antibody treatment. It has been demonstrated by our group and others, that spermidine – a naturally occurring polyamine, has the ability to activate PTPN2, leading to anti-inflammatory effects in vitro and in vivo (Moron, B., et al., PLoS One, 2013; Penrose, H.M., et al., J Biol Chem, 2013). Thus, the aim of this project is to investigate whether PTPN2 activation via spermidine treatment represents a novel therapeutic strategy for the treatment of IBD.