上皮内淋巴细胞（IEL）的积累是犬慢性肠病（CE）的组织病理学特征，并且IEL被认为是肠T细胞淋巴瘤（ITCL）的起源细胞。然而，CE 中 IEL 激活的致病机制仍不清楚。本研究假设，与细胞毒性 T/NK 细胞激活相关的促炎细胞因子的表达在 CE 和 ITCL 中上调，并检测了 IFN-γ、IL-2、IL-12p35、IL-12p40、IL-12 的表达。 15、无病变犬十二指肠粘膜中的 IL-21 和下游信号转导和转录激活因子 (STAT) 通路 (n = 11; NC)，与 IEL-CE (n = 19; CE 无上皮内淋巴细胞增多症)， IEL CE（n = 29；CE 伴有上皮内淋巴细胞增多）和 ITCL（n = 60）。定量聚合酶链反应 (PCR) 显示，IEL CE 中的 IFN-γ 和 IL-21 高于 IEL-CE 或 NC。 Western blot 显示 IEL CE 中 STAT1 和 STAT3 上调。双标记免疫组化显示CD3 T细胞的Ki67指数与IFN-γ表达水平呈正相关。免疫组织化学显示，IEL CE 和 ITCL 中 p-STAT1 阳性绒毛的比例高于 IEL-CE 和 NC，且与 IFN-γ 表达水平呈正相关。 60例ITCL病例中，肿瘤淋巴细胞p-STAT1免疫阳性28例，p-STAT3免疫阳性29例。这些结果表明IFN-γ和IL-21参与了IEL CE的发病机制，并且IFN-γ可能参与了CE中的T细胞活化和粘膜损伤。 ITCL 细胞中 STAT1 和 STAT3 的激活表明 STAT 通路上调在 ITCL 发病机制中发挥作用。

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-γ, 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-CE (n = 19; CE without intraepithelial lymphocytosis), IEL+CE (n = 29; CE with intraepithelial lymphocytosis), and with ITCL (n = 60). Quantitative polymerase chain reaction (PCR) revealed that IFN-γ and IL-21 were higher in IEL+CE than in IEL-CE or NC. Western blot revealed upregulation of STAT1 and STAT3 in IEL+CE. Double-labeling immunohistochemistry revealed a positive correlation between the Ki67 index of CD3+ T-cells and IFN-γ expression levels. Immunohistochemistry revealed a higher ratio of p-STAT1-positive villi in IEL+CE and ITCL than IEL-CE and NC, which positively correlated with IFN-γ 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-γ and IL-21 contribute to the pathogenesis of IEL+CE, and IFN-γ 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.