Pro-inflammatory cytokine expression and the STAT1/3 pathway in canine chronic enteropathy and intestinal T-cell lymphoma.

Abstract

The accumulation of intraepithelial lymphocytes (IELs) is a histopathological feature of canine chronic enteropathy (CE), and IELs are considered the cells of origin of intestinal T-cell lymphoma (ITCL). However, the pathogenic mechanism of IEL activation in CE remains unclear. This study hypothesized that the expression of proinflammatory cytokines, associated with cytotoxic T/NK-cell activation, is upregulated in CE and ITCL, and examined the expression of,,,, andand the downstream signal transducers and activators of transcription (STAT) pathway in the duodenal mucosa of dogs without lesions (= 11; NC), with IELCE (= 19; CE without intraepithelial lymphocytosis), IELCE (= 29; CE with intraepithelial lymphocytosis), and with ITCL (= 60). Quantitative polymerase chain reaction (PCR) revealed thatandwere higher in IELCE than in IELCE or NC. Western blot revealed upregulation of STAT1 and STAT3 in IELCE. Double-labeling immunohistochemistry revealed a positive correlation between the Ki67 index of CD3T-cells andexpression levels. Immunohistochemistry revealed a higher ratio of p-STAT1-positive villi in IELCE and ITCL than IELCE and NC, which positively correlated withexpression levels. Among the 60 ITCL cases, neoplastic lymphocytes were immunopositive for p-STAT1 in 28 cases and p-STAT3 in 29 cases. These results suggest thatandcontribute to the pathogenesis of IELCE, andmay be involved in T-cell activation and mucosal injury in CE. STAT1 and STAT3 activation in ITCL cells suggests a role for the upregulation of the STAT pathway in the pathogenesis of ITCL.