Department of Immunology, Medical University of Warsaw, 02-097 Warsaw, Poland.
Laboratory of Veterinary and Comparative Histopathology, Istituto Zooprofilattico Sperimentale Umbria e Marche "Togo Rosati", 06126 Perugia, Italy.
Int J Mol Sci. 2021 May 19;22(10):5358. doi: 10.3390/ijms22105358.
Inflammatory bowel disease is characterized by the infiltration of immune cells and chronic inflammation. The immune inhibitory receptor, CD200R, is involved in the downregulation of the activation of immune cells to prevent excessive inflammation. We aimed to define the role of CD200R ligand-CD200 in the experimental model of intestinal inflammation in conventionally-reared mice. Mice were given a dextran sodium sulfate solution in drinking water. Bodyweight loss was monitored daily and the disease activity index was calculated, and a histological evaluation of the colon was performed. TNF-α production was measured in the culture of small fragments of the distal colon or bone marrow-derived macrophages (BMDMs) cocultured with CD200 cells. We found that mice displayed diminished severity of colitis when compared to WT mice. Inflammation significantly diminished CD200 expression in WT mice, particularly on vascular endothelial cells and immune cells. The co-culture of BMDMs with CD200 cells inhibited TNF-α secretion. In vivo, acute colitis induced by DSS significantly increased TNF-α secretion in colon tissue in comparison to untreated controls. However, mice secreted a similar level of TNF-α to WT mice in vivo. CD200 regulates the severity of DSS-induced colitis in conventionally-reared mice. The presence of CD200 cells decreases TNF-α production by macrophages in vitro. However, during DDS-induced intestinal inflammation secretion of TNF-α is independent of CD200 expression.
炎症性肠病的特征是免疫细胞浸润和慢性炎症。免疫抑制受体 CD200R 参与下调免疫细胞的激活，以防止过度炎症。我们旨在确定 CD200 配体-CD200 在常规饲养小鼠的肠道炎症实验模型中的作用。将葡聚糖硫酸钠溶液给予小鼠饮用水。每天监测体重减轻并计算疾病活动指数，并对结肠进行组织学评估。测量远端结肠小片段或与 CD200 细胞共培养的骨髓来源巨噬细胞 (BMDM) 中的 TNF-α 产生。我们发现与 WT 小鼠相比， 小鼠的结肠炎严重程度降低。WT 小鼠的炎症明显降低了 CD200 的表达，尤其是在血管内皮细胞和免疫细胞上。BMDM 与 CD200 细胞的共培养抑制了 TNF-α 的分泌。在体内，与未处理的对照相比，DSS 诱导的急性结肠炎显著增加了结肠组织中 TNF-α 的分泌。然而， 小鼠体内 TNF-α 的分泌水平与 WT 小鼠相似。CD200 调节常规饲养小鼠 DSS 诱导的结肠炎的严重程度。CD200 细胞的存在减少了体外巨噬细胞中 TNF-α 的产生。然而，在 DDS 诱导的肠道炎症期间，TNF-α 的分泌不依赖于 CD200 表达。
