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 CD45RB^hi-naive CD4⁺ T cells from CK2α^fl/fl controls and CK2α^fl/fldLck-Cre mice into Rag1^−/− mice. CD4⁺ T cells from CK2α^fl/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.

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。