{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T06:28:43Z","timestamp":1787639323780,"version":"build-2736575974"},"reference-count":52,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Japan Society for the Promotion of Science","award":["19H03122"],"award-info":[{"award-number":["19H03122"]}]},{"name":"Japan Society for the Promotion of Science","award":["23KJ0671"],"award-info":[{"award-number":["23KJ0671"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Vet Pathol"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:p>\n                    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 IFN-\u03b3, IL-2, IL-12p35, IL-12p40, IL-15, and IL-21 and the downstream signal transducers and activators of transcription (STAT) pathway in the duodenal mucosa of dogs without lesions ( n = 11; NC), with IEL\n                    <jats:sup>\u2013<\/jats:sup>\n                    CE ( n = 19; CE without intraepithelial lymphocytosis), IEL\n                    <jats:sup>+<\/jats:sup>\n                    CE ( n = 29; CE with intraepithelial lymphocytosis), and with ITCL ( n = 60). Quantitative polymerase chain reaction (PCR) revealed that IFN-\u03b3 and IL-21 were higher in IEL\n                    <jats:sup>+<\/jats:sup>\n                    CE than in IEL\n                    <jats:sup>\u2013<\/jats:sup>\n                    CE or NC. Western blot revealed upregulation of STAT1 and STAT3 in IEL\n                    <jats:sup>+<\/jats:sup>\n                    CE. Double-labeling immunohistochemistry revealed a positive correlation between the Ki67 index of CD3\n                    <jats:sup>+<\/jats:sup>\n                    T-cells and IFN-\u03b3 expression levels. Immunohistochemistry revealed a higher ratio of p-STAT1-positive villi in IEL\n                    <jats:sup>+<\/jats:sup>\n                    CE and ITCL than IEL\n                    <jats:sup>\u2013<\/jats:sup>\n                    CE and NC, which positively correlated with IFN-\u03b3 expression 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 that IFN-\u03b3 and IL-21 contribute to the pathogenesis of IEL\n                    <jats:sup>+<\/jats:sup>\n                    CE, and IFN-\u03b3 may 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.\n                  <\/jats:p>","DOI":"10.1177\/03009858231207017","type":"journal-article","created":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T13:21:31Z","timestamp":1698758491000},"page":"382-392","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Pro-inflammatory cytokine expression and the STAT1\/3 pathway in canine chronic enteropathy and intestinal T-cell lymphoma"],"prefix":"10.1177","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0254-4979","authenticated-orcid":false,"given":"Kazuhiro","family":"Kojima","sequence":"first","affiliation":[{"name":"The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5273-7221","authenticated-orcid":false,"given":"James 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