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CCL17：一种具有多生物学功能的趋化因子
253 人阅读发布时间：2025-06-13 09:55
1. CCL17概述
CCL17（也称为TARC）是一种属于CC亚家族的趋化因子，主要参与免疫细胞的迁移、激活和炎症反应的调节。它由树突状细胞、内皮细胞、角质形成细胞和成纤维细胞等产生，并在胸腺中高表达，对T细胞的发育、迁移和成熟T细胞的激活起重要作用。CCL22和CCL17同属于CC型趋化因子家族，二者具有高度同源性，具有共同的受体分子CCR4，都可以有效趋化CCR4表达阳性的细胞。
Figure 1. CCL17二聚体结构，来源于PDB：1NR4。球体部分为G7T突变位置，绿色部分为二硫键位置。
来源：DOI: 10.1016/j.bbrep.2017.11.005
2. CCL17与疾病的关联
2.1 心血管疾病
CCL17在心血管疾病中起着关键作用，尤其是在年龄相关和血管紧张素II (Ang II)诱导的病理性心脏重塑和心力衰竭中。研究发现，随着年龄的增长，血清中CCL17水平显著增加，并与心脏功能障碍相关。在动物实验中，CCL17基因敲除小鼠显示出对年龄和Ang II诱导的心脏肥大和纤维化的抑制作用，并伴随着T细胞亚群的可塑性和分化 [1]。此外，使用抗CCL17中和抗体的治疗也显著抑制了Ang II诱导的病理性心脏重塑 [2]。这些发现揭示了CCL17作为一种新的治疗靶点的潜力，可用于年龄相关和Ang II诱导的病理性心脏肥大和心力衰竭。
2.2 炎症与自身免疫性疾病
趋化因子受体CCR4是CCL17的高亲和力受体，CCL17在炎症中的作用主要体现在其通过与CCR4结合，参与调控炎症反应和炎症性疼痛。在炎症模型中，CCL17能够促进炎症性T细胞的趋化和激活，尤其是在Th2型免疫反应中 [3]。在骨关节炎模型中，CCL17基因敲除小鼠显示出对疼痛和疾病发展的抵抗性，表明CCL17在炎症性疼痛的发病机制中起着关键作用 [4]。此外，在炎症性关节炎和肠道炎症模型中，CCL17的缺乏也能够减轻疾病症状，进一步支持了CCL17在炎症中的重要作用 [5][6]。
在自身免疫疾病中，CCL17同样扮演着重要角色 [3]。在系统性红斑狼疮（SLE）中，CCL17的表达也有所增加，提示其可能参与SLE的免疫病理过程 [7][8]。此外，在多发性硬化症（MS）的动物模型实验性自身免疫性脑脊髓炎（EAE）中，CCL17基因敲除小鼠显示出减轻的疾病症状 [9]。这些研究结果表明，CCL17在自身免疫疾病的发病机制中具有重要作用，并可能成为治疗这些疾病的新靶点。
CCL17在过敏性哮喘中发挥着关键作用，它由树突状细胞（DCs）产生，能吸引Th2细胞到气道，引发过敏性哮喘的炎症反应。NOD1刺激的树突状细胞在体内能加重Th2肺部反应，且这种作用以CCL17依赖性方式发生 [10]。通过人源化SCID小鼠模型的研究发现，阻断CCR4（CCL17的受体）能显著减少气道炎症和支气管高反应性，表明CCR4-CCL17轴在Th2细胞招募到气道中起到关键作用 [11]。这些研究结果都暗示了CCL17可能是一个潜在的治疗过敏性哮喘的靶点。
2.3 肿瘤及肿瘤微环境
CCL17在多种肿瘤细胞中高表达，能促进肿瘤细胞增殖、迁移和侵袭。在肝细胞癌中，与M2型巨噬细胞共培养或用CCL17处理，可增强肿瘤细胞的这些恶性生物学行为，还能提升细胞干性，促进肿瘤球形成，并上调肿瘤干细胞相关转录因子表达，助力肿瘤复发和转移 [12]。此外，CCL17通过激活TGF-β1/Smad和Wnt/β-catenin信号通路，影响上皮-间质转化过程，进一步加强肿瘤细胞的侵袭和转移能力 [13]。
CCL17与多种免疫细胞浸润相关。在胃癌和甲状腺癌中，其高表达与Foxp3+调节性T细胞聚集有关，可能抑制抗肿瘤免疫 [13][14]。同时，CCR4-CCL17信号轴选择性招募Th2细胞、Tregs、记忆T细胞至炎症或肿瘤微环境，通过JAK/STAT6、PI3K/AKT通路激活免疫抑制程序。
3. 相关信号通路研究
| 信号通路/分子 | 作用描述 | 相关疾病/细胞类型 | 参考文献 |
|---|---|---|---|
| CCL17/CCR4 | 促进肿瘤细胞迁移、侵袭、干性维持，调控免疫细胞迁移 | 多种肿瘤、干细胞 | 12, 15, 16, 17, 18 |
| ERK/PD-L1 | CCL17通过CCR4激活ERK/PD-L1信号，增强肿瘤细胞恶性行为 | 食管鳞癌 | 15 |
| mTORC1/mTORC2 | 乳酸诱导M2极化，M2分泌CCL17，CCL17/CCR4激活mTORC1促进肿瘤侵袭 | 垂体腺瘤 | 16, 19 |
| Wnt/β-catenin、TGF-β1 | CCL17促进肿瘤细胞EMT及干性，激活Wnt/β-catenin和TGF-β1信号 | 肝细胞癌 | 12 |
| STAT6/IRF4/JMJD3 | IL-4诱导CCL17表达依赖STAT6-IRF4-JMJD3通路，涉及表观遗传调控 | 单核细胞/巨噬细胞 | 7 |
| β-arrestin | CCL17激活CCR4主要招募β-arrestin而非G蛋白，提示其可能作为清道夫受体 | T细胞 | 20 |
4. 临床意义与应用前景
4.1 生物标志物与预后预测
CCL17/CCL22高表达可预测头颈鳞癌患者的免疫检查点抑制剂疗效及生存率 [19]，在鼻型NK/T细胞淋巴瘤、肝癌等疾病中也有潜在的诊断和预后价值 [12][18]。
4.2 靶向治疗潜力
抗CCR4单抗可介导NK细胞杀伤肿瘤细胞，CCL17/CCR4轴成为多种肿瘤的新型靶向治疗候选 [18][21]。
5. 相关产品推荐
华美生物提供CCL17相关高质量重组蛋白和抗体，旨在帮助科研工作者进行CCL17作用机制与临床转化方向的研究：
● CCL17重组蛋白
Recombinant Human C-C motif chemokine 17 (CCL17) (Active); CSB-MP856406HU
Recombinant Macaca mulatta C-C motif chemokine 17 (CCL17) (Active); CSB-MP811562MOW
Recombinant Mouse C-C motif chemokine 17 (Ccl17) (Active); CSB-MP6512MO
● CCL17重组抗体
CCL17 Recombinant Monoclonal Antibody; CSB-RA856406MA1HU
Activity: Measured by its binding ability in a functional ELISA. Immobilized Anti-CCL17 recombinant antibody at 2 μg/mL can bind Human CCL17 protein (CSB-MP856406HU). The EC50 is 2.403-2.741 ng/mL.
● CCL17(TRAC) ELISA试剂盒
Human thymus activation regulated chemokine,TARC/CCL17 ELISA Kit; CSB-E09257h
Monkey C-C motif chemokine 17(CCL17) ELISA kit; CSB-EL004780RH
Canine thymus activation regulated chemokine(TARC/CCL17)ELISA Kit; CSB-E17792c
参考文献：
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