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Modulation of Human Immune Responses by Bovine Interleukin-10

机译:牛白介素10对人体免疫应答的调节

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摘要

Cytokines can be functionally active across species barriers. Bovine IL-10 has an amino acid sequence identity with human IL-10 of 76.8%. Therefore, the aim of this study was to evaluate whether bovine IL-10 has immunomodulatory activities on human monocytes and dendritic cells. Peripheral blood monocytes were isolated from healthy donors, and used directly or allowed to differentiate to dendritic cells under the influence of IL-4 and GM-CSF. Recombinant bovine IL-10 inhibited TLR induced activation of monocytes, and dose-dependently inhibited LPS-induced activation of monocyte-derived DCs comparable to human IL-10. By using blocking antibodies to either bovine IL-10 or the human IL-10 receptor it was demonstrated that inhibition of monocyte activation by bovine IL-10 was dependent on binding of bovine IL-10 to the human IL-10R. These data demonstrate that bovine IL-10 potently inhibits the activation of human myeloid cells in response to TLR activation. Bovine IL-10 present in dairy products may thus potentially contribute to the prevention of necrotizing enterocolitis and allergy, enhance mucosal tolerance induction and decrease intestinal inflammation and may therefore be applicable in infant foods and in immunomodulatory diets.
机译:细胞因子可以跨物种屏障发挥功能活性。牛IL-10与人IL-10的氨基酸序列同一性为76.8%。因此,本研究的目的是评估牛IL-10是否对人单核细胞和树突状细胞具有免疫调节活性。从健康供体中分离出外周血单核细胞,并在IL-4和GM-CSF的影响下直接使用或使其分化为树突状细胞。与人IL-10相比,重组牛IL-10抑制了TLR诱导的单核细胞活化,并剂量依赖性地抑制了LPS诱导的单核细胞衍生DC活化。通过使用针对牛IL-10或人IL-10受体的阻断抗体,证明了牛IL-10对单核细胞活化的抑制依赖于牛IL-10与人IL-10R的结合。这些数据证明,牛IL-10响应TLR活化而有效抑制人骨髓细胞的活化。因此,乳制品中存在的牛IL-10可能潜在地有助于预防坏死性小肠结肠炎和变态反应,增强粘膜耐受性诱导并减少肠道炎症,因此可用于婴儿食品和免疫调节饮食。

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