Department of Gastroenterology (South Building), China PLA General Hospital, Beijing, China.
J Leukoc Biol. 2011 Jan;89(1):85-91. doi: 10.1189/jlb.0910506. Epub 2010 Oct 15.
The pathogenesis of CRC remains to be further understood. This study was designed to elucidate the role of Foxp3+IL-17+ T cells in the pathogenesis of CRC. Surgically removed CRC tissue was collected from 12 patients with CRC. The frequency and cytokine profile of Foxp3+IL-17+ T cells in CRC were examined by flow cytometry. Chemokine CXCL11 was examined in CRC tissue by Western blotting. Treg chemotaxis was examined in a transwell system. The effect of Foxp3+IL-17+ T cells on induction of cancer-initiating cells was examined; the latter's Akt and MAPK activities and colony formation were examined afterward. Abundant Foxp3+IL-17+ T cells were detected in CRC tissue that expresses high levels of TGF-β, CXCR3, CCR6, and RORγt. High levels of CXCL11 were detected in CRC tissue-derived CD68+ cells, which had a strong chemotactic effect on Foxp3+ Tregs. Hypoxia induced the expression of IL-17 in Foxp3+ Tregs; Foxp3+IL-17+ T cells were capable of inducing CRC-associated cell markers in BMMo and drove the cells to be cancer-initiating cells. High levels of phosphorylated Akt and MAPK were detected in the induced cancer-initiation cells; the latter has the capability to form a colony. CRC tissue-derived Foxp3+IL-17+ cells have the capacity to induce cancer-initiating cells.
CRC 的发病机制仍有待进一步阐明。本研究旨在阐明 Foxp3+IL-17+T 细胞在 CRC 发病机制中的作用。从 12 名 CRC 患者中采集手术切除的 CRC 组织。通过流式细胞术检测 CRC 中 Foxp3+IL-17+T 细胞的频率和细胞因子谱。通过 Western blot 检测 CRC 组织中的趋化因子 CXCL11。通过 Transwell 系统检测 Treg 趋化性。检测 Foxp3+IL-17+T 细胞对诱导癌症起始细胞的影响；随后检测后者的 Akt 和 MAPK 活性和集落形成。在表达高水平 TGF-β、CXCR3、CCR6 和 RORγt 的 CRC 组织中检测到大量 Foxp3+IL-17+T 细胞。在 CRC 组织衍生的 CD68+细胞中检测到高水平的 CXCL11，其对 Foxp3+Tregs 具有强烈的趋化作用。缺氧诱导 Foxp3+Tregs 中 IL-17 的表达；Foxp3+IL-17+T 细胞能够在 BMMo 中诱导 CRC 相关细胞标志物，并促使细胞成为癌症起始细胞。在诱导的起始癌细胞中检测到高磷酸化 Akt 和 MAPK；后者具有形成集落的能力。CRC 组织衍生的 Foxp3+IL-17+细胞具有诱导癌症起始细胞的能力。
