PTPN22 and the pathogenesis of ulcerative colitis: Insights into T cell differentiation and the JAK/STAT signaling pathway

Abstract

70 % of the ulcerative colitis (UC) linked gene loci are associated with other autoimmune or immunodeficient diseases. The phosphatase activity of PTPN22 can regulate the development of T cells and contribute to regulate the level of inflammation in autoimmune diseases. We produced PTPN22-CS thymus-specific transgenic mice, which suppressed PTPN22 enzyme activity in the thymocytes. Overexpressed PTPN22-CS facilitated the development of the thymocytes towards CD4⁺T cells and resulted in an increased proportion of the Th1 and Treg cells in the UC mesenteric lymph nodes. PTPN22-CS promoted the activation of the JAK/STAT signaling pathway in the Th1 and Treg cells that localized in the colon, resulting in an excessive production of inflammatory mediators such as IL-2 and IFN-γ. Consequently, PTPN22-CS contributes to the inflammatory response of ulcerative colitis. In summary, the tyrosine phosphatase activity of PTPN22 plays a role in modulating UC by regulating T cell differentiation and modulating the JAK/STAT signaling pathway, thereby influencing the inflammatory response in colonic. These findings provide new insight into the association between PTPN22 and the pathogenesis of UC.