Inflammatory colorectal polyp (ICRP) is an emerging disease in Miniature Dachshunds (MDs). Animals with this disease exhibit multiple polyps with severe neutrophil infiltration that respond to immunosuppressive therapy. Macrophages in polypoid lesions have been described to play an important role in neutrophil infiltration in the lesion by producing IL-8. In contrast, IL-10, an anti-inflammatory cytokine, was also reported to be upregulated in polypoid lesions, but its significance in the pathogenesis of ICRP has not been clarified. Regulatory T cells (Tregs) are the main source of IL-10 production and contribute to the maintenance of intestinal homeostasis. Therefore, the objective of this research was to compare the distribution of Tregs in polypoid lesions of ICRPs and the association between the distribution and expression of pro- or anti-inflammatory cytokines. Tissue biopsy specimens of polypoid lesions were collected from 28 MDs with ICRP. Those of macroscopically non-polypoid colonic mucosa from 24 MDs with ICRPs and 21 control dogs were further included as controls. Real-time quantitative polymerase chain reaction was used to quantify gene expression of IL-1β, IL-4, IL-6, IL-8, IL-10, IL-17, IL-22, IFN-γ, TNF-α, TGF-β, and forkhead box protein P3 (Foxp3) in each tissue sample. The numbers of Foxp3-positive cells (Tregs) and ionized calcium binding adapter molecule 1 (Iba-1)-positive cells (macrophages) were determined by immunohistochemistry. The gene expression of IL-1β, IL-6, IL-8, TNF-α, IFN-γ, IL-17, IL-10, TGF-β, and Foxp3 was significantly upregulated in polypoid lesions relative to control levels. The numbers of Foxp3-positive Tregs and Iba-1-positive macrophages were significantly increased in polypoid lesions compared to those in the non-polypoid colonic mucosa of MDs with ICRPs and control dogs. The upregulation of IL-10 was moderately correlated with the distribution of Tregs in polypoid lesions from MDs with ICRPs. In addition, the relative upregulation of IL-1β, IL-6, and IL-8 in polypoid lesions, compared to expression in non-polypoid colonic mucosa of MDs with ICRPs, was significantly greater than that of IL-10. These results indicate that increases in Treg numbers and anti-inflammatory cytokines in polypoid lesions comprise reactive changes in response to the inflammation, which warrants further investigation.

中文翻译：

---

调节性T细胞在小型腊肠犬发炎的大肠息肉中的分布。

炎症性结肠直肠息肉（ICRP）是小型腊肠犬（MDs）中的一种新兴疾病。患有这种疾病的动物表现出多发性息肉，中性粒细胞浸润严重，对免疫抑制疗法有反应。据报道，息肉样病变中的巨噬细胞通过产生IL-8在病变的嗜中性粒细胞浸润中起重要作用。相比之下，据报道IL-10（一种抗炎细胞因子）在息肉样病变中也被上调，但其在ICRP发病机理中的意义尚不清楚。调节性T细胞（Tregs）是IL-10产生的主要来源，并有助于维持肠内稳态。因此，本研究的目的是比较Tregs在ICRP息肉样病变中的分布以及促炎或抗炎细胞因子的分布与表达之间的联系。使用ICRP从28个MD中收集息肉样病变的组织活检标本。作为对照，进一步包括来自24只具有ICRPs的MD的宏观非息肉状结肠粘膜和21只对照犬的那些。实时定量聚合酶链反应用于量化IL-1β，IL-4，IL-6，IL-8，IL-10，IL-17，IL-22，IFN-γ，TNF-α， TGF-β和每个组织样本中的叉头盒蛋白P3（Foxp3）。通过免疫组织化学测定Foxp3阳性细胞（Tregs）和离子化钙结合衔接子分子1（Iba-1）阳性细胞（巨噬细胞）的数目。IL-1β，IL-6，IL-8，TNF-α，IFN-γ，相对于对照水平，息肉样病变中的IL-17，IL-10，TGF-β和Foxp3明显上调。与具有ICRPs和对照犬的MDs的非息肉样结肠黏膜相比，息肉样病变中Foxp3阳性Treg和Iba-1阳性巨噬细胞的数量显着增加。IL-10的上调与TRPs在ICRPs的MDs的息肉样病变中的分布适度相关。另外，与ICRPs的MDs在非息肉状结肠粘膜中的表达相比，息肉状病变中IL-1β，IL-6和IL-8的相对上调显着大于IL-10。这些结果表明，息肉样病灶中Treg数量的增加和抗炎细胞因子包括对炎症反应的反应性变化，这值得进一步研究。与息肉对照相比，息肉样病变中Foxp3明显上调。与具有ICRPs和对照犬的MDs的非息肉样结肠黏膜相比，息肉样病变中Foxp3阳性Treg和Iba-1阳性巨噬细胞的数量显着增加。IL-10的上调与TRPs在ICRPs的MDs的息肉样病变中的分布适度相关。另外，与ICRPs的MDs在非息肉状结肠粘膜中的表达相比，息肉状病变中IL-1β，IL-6和IL-8的相对上调显着大于IL-10。这些结果表明，息肉样病灶中Treg数量的增加和抗炎细胞因子包括对炎症反应的反应性变化，这值得进一步研究。与息肉对照相比，息肉样病变中Foxp3明显上调。与具有ICRPs和对照犬的MDs的非息肉样结肠黏膜相比，息肉样病变中Foxp3阳性Treg和Iba-1阳性巨噬细胞的数量显着增加。IL-10的上调与TRPs在ICRPs的MDs的息肉样病变中的分布适度相关。另外，与ICRPs的MDs在非息肉状结肠粘膜中的表达相比，息肉状病变中IL-1β，IL-6和IL-8的相对上调显着大于IL-10。这些结果表明，息肉样病灶中Treg数量的增加和抗炎细胞因子包括对炎症反应的反应性变化，这值得进一步研究。