Amphiregulin enhances regulatory T cell-suppressive function via the epidermal growth factor receptor.

Amphiregulin enhances regulatory T cell-suppressive function via the epidermal growth factor receptor.
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DOI:
10.1016/j.immuni.2012.09.023
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发表时间:
2013-02-21
期刊:
影响因子:
32.4
通讯作者:
Sijts AJ
Sijts AJ
中科院分区:
医学1区
文献类型:
--
作者:
Zaiss DM;van Loosdregt J;Gorlani A;Bekker CP;Gröne A;Sibilia M;van Bergen en Henegouwen PM;Roovers RC;Coffer PJ;Sijts AJ

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表皮生长因子受体(EGFR)是已知的关键参与组织发育和稳态,以及在癌症的发病机制。在这里,我们发现Foxp3+调节性T(Treg)细胞在炎症条件下表达EGFR。用EGF样生长因子双调蛋白(AREG)刺激显著增强体外Treg细胞功能,并且在结肠炎和肿瘤疫苗接种模型中,我们表明AREG对于体内有效的Treg细胞功能至关重要。此外,肥大细胞衍生的AREG完全恢复了最佳Treg细胞功能。这些发现揭示了EGFR作为调节局部免疫应答的组分,并建立了肥大细胞和Treg细胞之间的联系。靶向这种免疫调节机制可能有助于EGFR靶向治疗在癌症患者中的治疗成功。
Epidermal growth factor receptor (EGFR) is known to be critically involved in tissue development and homeostasis as well as in the pathogenesis of cancer. Here we showed that Foxp3+ regulatory T (Treg) cells express EGFR under inflammatory conditions. Stimulation with the EGF-like growth factor Amphiregulin (AREG) markedly enhanced Treg cell function in vitro, and in a colitis and tumor vaccination model we showed that AREG was critical for efficient Treg cell function in vivo. In addition, mast cell-derived AREG fully restored optimal Treg cell function. These findings reveal EGFR as a component in the regulation of local immune responses and establish a link between mast cells and Treg cells. Targeting of this immune regulatory mechanism may contribute to the therapeutic successes of EGFR-targeting treatments in cancer patients.
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