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Protein kinase 2 (CK2) controls CD4+ T cell effector function in the pathogenesis of colitis.
Mucosal Immunology ( IF 7.9 ) Pub Date : 2020-01-27 , DOI: 10.1038/s41385-020-0258-x
Wei Yang 1 , Sara A Gibson 2 , Zhaoqi Yan 1 , Hairong Wei 1 , Jiahui Tao 1 , Bingdong Sha 1 , Hongwei Qin 1 , Etty N Benveniste 1
Affiliation  

Crohn’s disease (CD), one of the major forms of inflammatory bowel disease (IBD), is characterized by chronic inflammation of the gastrointestinal tract and associated with aberrant CD4+ T-helper type 1 (Th1) and Th17 responses. Protein kinase 2 (CK2) is a conserved serine–threonine kinase involved in signal transduction pathways, which regulate immune responses. CK2 promotes Th17 cell differentiation and suppresses the generation of Foxp3+ regulatory T cells. The function of CK2 in CD4+ T cells during the pathogenesis of CD is unknown. We utilized the T cell-induced colitis model, transferring CD45RBhi-naive CD4+ T cells from CK2αfl/fl controls and CK2αfl/fldLck-Cre mice into Rag1−/− mice. CD4+ T cells from CK2αfl/fldLck-Cre mice failed to induce wasting disease and significant intestinal inflammation, which was associated with decreased interleukin-17A-positive (IL-17A+), interferon-γ-positive (IFN-γ+), and double-positive IL-17A+IFN-γ+ CD4+ T cells in the spleen and colon. We determined that CK2α regulates CD4+ T cell proliferation through a cell-intrinsic manner. CK2α is also important in controlling CD4+ T cell responses by regulating NFAT2, which is vital for T cell activation and proliferation. Our findings indicate that CK2α contributes to the pathogenesis of colitis by promoting CD4+ T cell proliferation and Th1 and Th17 responses, and that targeting CK2 may be a novel therapeutic treatment for patients with CD.



中文翻译:

蛋白激酶 2 (CK2) 在结肠炎的发病机制中控制 CD4+ T 细胞效应子功能。

克罗恩病 (CD) 是炎症性肠病 (IBD) 的主要形式之一,其特征是胃肠道慢性炎症,并与异常的 CD4 + T 辅助细胞 1 型 (Th1) 和 Th17 反应相关。蛋白激酶 2 (CK2) 是一种保守的丝氨酸-苏氨酸激酶,参与调节免疫反应的信号转导通路。CK2 促进 Th17 细胞分化并抑制 Foxp3 +调节性 T 细胞的产生。CD 发病机制中 CD4 + T 细胞中CK2 的功能尚不清楚。我们利用 T 细胞诱导的结肠炎模型,从 CK2α fl/fl对照和 CK2α fl/fl转移 CD45RB hi -naive CD4 + T 细胞dLck-Cre 小鼠变成 Rag1 -/-小鼠。来自 CK2α fl/fl dLck-Cre 小鼠的CD4 + T 细胞未能诱导消耗性疾病和显着的肠道炎症,这与白细胞介素 17A 阳性 (IL-17A + )、干扰素-γ 阳性 (IFN-γ + ),以及脾脏和结肠中的双阳性 IL-17A + IFN-γ + CD4 + T 细胞。我们确定 CK2α通过细胞固有方式调节 CD4 + T 细胞增殖。CK2α 在控制 CD4 +方面也很重要T 细胞通过调节 NFAT2 进行反应,NFAT2 对于 T 细胞活化和增殖至关重要。我们的研究结果表明,CK2α 通过促进 CD4 + T 细胞增殖和 Th1 和 Th17 反应促进结肠炎的发病机制,靶向 CK2 可能是 CD 患者的一种新型治疗方法。

更新日期:2020-01-27
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