CCL17：一種具有多生物學功能的趨化因子
日期：2025-06-09 09:38:02
1. CCL17概述
CCL17（也稱為TARC）是一種屬于CC亞家族的趨化因子，主要參與免疫細胞的遷移、激活和炎癥反應的調節。它由樹突狀細胞、內皮細胞、角質形成細胞和成纖維細胞等產生，并在胸腺中高表達，對T細胞的發育、遷移和成熟T細胞的激活起重要作用。CCL22和CCL17同屬于CC型趨化因子家族，二者具有高度同源性，具有共同的受體分子CCR4，都可以有效趨化CCR4表達陽性的細胞。
Figure 1. CCL17二聚體結構，來源于PDB：1NR4。球體部分為G7T突變位置，綠色部分為二硫鍵位置。
來源：DOI: 10.1016/j.bbrep.2017.11.005
2. CCL17與疾病的關聯
2.1 心血管疾病
CCL17在心血管疾病中起著關鍵作用，尤其是在年齡相關和血管緊張素II (Ang II)誘導的病理性心臟重塑和心力衰竭中。研究發現，隨著年齡的增長，血清中CCL17水平顯著增加，并與心臟功能障礙相關。在動物實驗中，CCL17基因敲除小鼠顯示出對年齡和Ang II誘導的心臟肥大和纖維化的抑制作用，并伴隨著T細胞亞群的可塑性和分化 [1]。此外，使用抗CCL17中和抗體的治療也顯著抑制了Ang II誘導的病理性心臟重塑 [2]。這些發現揭示了CCL17作為一種新的治療靶點的潛力，可用于年齡相關和Ang II誘導的病理性心臟肥大和心力衰竭。
2.2 炎癥與自身免疫性疾病
趨化因子受體CCR4是CCL17的高親和力受體，CCL17在炎癥中的作用主要體現在其通過與CCR4結合，參與調控炎癥反應和炎癥性疼痛。在炎癥模型中，CCL17能夠促進炎癥性T細胞的趨化和激活，尤其是在Th2型免疫反應中 [3]。在骨關節炎模型中，CCL17基因敲除小鼠顯示出對疼痛和疾病發展的抵抗性，表明CCL17在炎癥性疼痛的發病機制中起著關鍵作用 [4]。此外，在炎癥性關節炎和腸道炎癥模型中，CCL17的缺乏也能夠減輕疾病癥狀，進一步支持了CCL17在炎癥中的重要作用 [5][6]。
在自身免疫疾病中，CCL17同樣扮演著重要角色 [3]。在系統性紅斑狼瘡（SLE）中，CCL17的表達也有所增加，提示其可能參與SLE的免疫病理過程 [7][8]。此外，在多發性硬化癥（MS）的動物模型實驗性自身免疫性腦脊髓炎（EAE）中，CCL17基因敲除小鼠顯示出減輕的疾病癥狀 [9]。這些研究結果表明，CCL17在自身免疫疾病的發病機制中具有重要作用，并可能成為治療這些疾病的新靶點。
CCL17在過敏性哮喘中發揮著關鍵作用，它由樹突狀細胞（DCs）產生，能吸引Th2細胞到氣道，引發過敏性哮喘的炎癥反應。NOD1刺激的樹突狀細胞在體內能加重Th2肺部反應，且這種作用以CCL17依賴性方式發生 [10]。通過人源化SCID小鼠模型的研究發現，阻斷CCR4（CCL17的受體）能顯著減少氣道炎癥和支氣管高反應性，表明CCR4-CCL17軸在Th2細胞招募到氣道中起到關鍵作用 [11]。這些研究結果都暗示了CCL17可能是一個潛在的治療過敏性哮喘的靶點。
2.3 腫瘤及腫瘤微環境
CCL17在多種腫瘤細胞中高表達，能促進腫瘤細胞增殖、遷移和侵襲。在肝細胞癌中，與M2型巨噬細胞共培養或用CCL17處理，可增強腫瘤細胞的這些惡性生物學行為，還能提升細胞干性，促進腫瘤球形成，并上調腫瘤干細胞相關轉錄因子表達，助力腫瘤復發和轉移 [12]。此外，CCL17通過激活TGF-β1/Smad和Wnt/β-catenin信號通路，影響上皮-間質轉化過程，進一步加強腫瘤細胞的侵襲和轉移能力 [13]。
CCL17與多種免疫細胞浸潤相關。在胃癌和甲狀腺癌中，其高表達與Foxp3+調節性T細胞聚集有關，可能抑制抗腫瘤免疫 [13][14]。同時，CCR4-CCL17信號軸選擇性招募Th2細胞、Tregs、記憶T細胞至炎癥或腫瘤微環境，通過JAK/STAT6、PI3K/AKT通路激活免疫抑制程序。
3. 相關信號通路研究
| 信號通路/分子 | 作用描述 | 相關疾病/細胞類型 | 參考文獻 |
|---|---|---|---|
| CCL17/CCR4 | 促進腫瘤細胞遷移、侵襲、干性維持，調控免疫細胞遷移 | 多種腫瘤、干細胞 | 12, 15, 16, 17, 18 |
| ERK/PD-L1 | CCL17通過CCR4激活ERK/PD-L1信號，增強腫瘤細胞惡性行為 | 食管鱗癌 | 15 |
| mTORC1/mTORC2 | 乳酸誘導M2極化，M2分泌CCL17，CCL17/CCR4激活mTORC1促進腫瘤侵襲 | 垂體腺瘤 | 16, 19 |
| Wnt/β-catenin、TGF-β1 | CCL17促進腫瘤細胞EMT及干性，激活Wnt/β-catenin和TGF-β1信號 | 肝細胞癌 | 12 |
| STAT6/IRF4/JMJD3 | IL-4誘導CCL17表達依賴STAT6-IRF4-JMJD3通路，涉及表觀遺傳調控 | 單核細胞/巨噬細胞 | 7 |
| β-arrestin | CCL17激活CCR4主要招募β-arrestin而非G蛋白，提示其可能作為清道夫受體 | T細胞 | 20 |
4. 臨床意義與應用前景
4.1 生物標志物與預后預測
CCL17/CCL22高表達可預測頭頸鱗癌患者的免疫檢查點抑制劑療效及生存率 [19]，在鼻型NK/T細胞淋巴瘤、肝癌等疾病中也有潛在的診斷和預后價值 [12][18]。
4.2 靶向治療潛力
抗CCR4單抗可介導NK細胞殺傷腫瘤細胞，CCL17/CCR4軸成為多種腫瘤的新型靶向治療候選 [18][21]。
5. 相關產品推薦
華美生物提供CCL17相關高質量重組蛋白和抗體，旨在幫助科研工作者進行CCL17作用機制與臨床轉化方向的研究：
● CCL17重組蛋白
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重組抗體
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試劑盒
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