Interleukin-13 is overexpressed in cutaneous T-cell lymphoma cells and regulates their proliferation
Interleukin-13 is overexpressed in cutaneous T-cell lymphoma cells and regulates their proliferation
复制标题
DOI：
10.1182/blood-2014-07-590398
复制
发表时间：
2015-04-30
期刊：
影响因子：
20.3
通讯作者：
Fuschiotti, Patrizia
中科院分区：
文献类型：
--
作者：
Geskin, Larisa J.;Viragova, Sara;Fuschiotti, Patrizia
皮肤t细胞淋巴瘤（CTCLs）主要影响皮肤，其特征是成熟CD4(+) t辅助细胞的增殖。皮肤和血液中细胞因子产生的模式被认为对ctcl的发病机制具有重要意义。细胞因子在ctcl中的异常表达可能是恶性细胞增殖增强和/或抗肿瘤免疫反应抑制的原因。本研究表明，白细胞介素-13 （IL-13）及其受体IL-13R α 1和IL-13R α 2在CTCL患者的临床受累皮肤中高度表达。我们还发现，在CTCL患者的皮肤和血液中，通过CD4和TOX（胸腺高流动性组框）的共表达来鉴定的恶性淋巴瘤细胞产生IL-13并表达这两种受体。IL-13通过IL-13R α 1诱导CTCL细胞体外生长和信号转导。此外，抗体介导的IL-13或可溶性IL-13R α 2分子的中和可导致肿瘤细胞增殖的抑制，暗示IL-13在CTCL中是一个自分泌因子。重要的是，我们确定了IL-13与IL-4协同抑制CTCL细胞生长，阻断IL-4/IL-13信号通路完全逆转肿瘤细胞增殖。我们得出结论，IL-13及其信号介质是CTCL恶性肿瘤的新标志物和潜在的干预治疗靶点。
Cutaneous T-cell lymphomas (CTCLs) primarily affect skin and are characterized by proliferation of mature CD4(+) T-helper cells. The pattern of cytokine production in the skin and blood is considered to be of major importance for the pathogenesis of CTCLs. Abnormalcytokine expression in CTCLs may be responsible for enhanced proliferation of the malignant cells and/or depression of the antitumor immune response. Here we show that interleukin-13 (IL-13) and its receptors IL-13R alpha 1 and IL-13R alpha 2 are highly expressed in the clinically involved skin of CTCL patients. We also show that malignant lymphoma cells, identified by the coexpression of CD4 and TOX (thymus high-mobility group box), in the skin and blood of CTCL patients produce IL-13 and express both receptors. IL-13 induces CTCL cell growth in vitro and signaling through the IL-13R alpha 1. Furthermore, antibody-mediated neutralization of IL-13 or soluble IL-13R alpha 2 molecules can lead to inhibition of tumor-cell proliferation, implicating IL-13 as an autocrine factor in CTCL. Importantly, we established that IL-13 synergizes with IL-4 in inhibiting CTCL cell growth and that blocking the IL-4/IL-13 signaling pathway completely reverses tumor-cell proliferation. We conclude that IL-13 and its signaling mediators are novel markers of CTCL malignancy and potential therapeutic targets for intervention.