CCL17/TARC 在自身免疫和炎症中的作用——不仅仅是 T 细胞趋化因子,Immunology and Cell Biology

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CCL17/TARC 在自身免疫和炎症中的作用——不仅仅是 T 细胞趋化因子
Immunology and Cell Biology ( IF 3.2 ) Pub Date : 2023-03-28 , DOI: 10.1111/imcb.12644
Tanya J Lupancu ₁ , Mahtab Eivazitork ₁ , John A Hamilton _{1,

2} , Adrian A Achuthan ₁ , Kevin M-C Lee ₁

Affiliation

趋化因子 (C–C) 配体 17 (CCL17) 在被发现在胸腺中组成型表达并被鉴定为 T 细胞趋化因子时首次被鉴定为胸腺和激活调节趋化因子。随后发现这种化学引诱分子在一系列自身免疫性疾病、炎症性疾病以及癌症中的水平升高。CCL17 是一种 C–C 趋化因子受体 4 型 (CCR4) 配体，趋化因子 (C–C) 配体 22 是另一个主要配体，并且由于 CCR4 在辅助 T 细胞上高表达，CCL17 可以在 T 细胞中发挥作用– 驱动的疾病，通常被认为是通过其对 T 辅助 2 细胞的趋化活性引起的；然而，鉴于 CCR4 也由其他细胞类型表达，并且 CCL17 在许多疾病中表达升高，因此建议更广泛的 CCL17 生物学。在这篇综述中，我们总结了 CCL17 的生物学、其调控及其对各种临床前模型发病机制的潜在贡献。例如，最近的文献表明，CCL17 在淋巴细胞非依赖性模型中作为粒细胞巨噬细胞集落刺激因子/CCL17 通路的一部分，在控制疼痛中发挥作用，因此不是 T 细胞趋化因子。该综述还讨论了 CCL17 作为人类疾病生物标志物和治疗靶点的潜力。

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CCL17/TARC in autoimmunity and inflammation—not just a T-cell chemokine

Chemokine (C–C) ligand 17 (CCL17) was first identified as thymus- and activation-regulated chemokine when it was found to be constitutively expressed in the thymus and identified as a T-cell chemokine. This chemoattractant molecule has subsequently been found at elevated levels in a range of autoimmune and inflammatory diseases, as well as in cancer. CCL17 is a C–C chemokine receptor type 4 (CCR4) ligand, with chemokine (C–C) ligand 22 being the other major ligand and, as CCR4 is highly expressed on helper T cells, CCL17 can play a role in T-cell–driven diseases, usually considered to be via its chemotactic activity on T helper 2 cells; however, given that CCR4 is also expressed by other cell types and there is elevated expression of CCL17 in many diseases, a broader CCL17 biology is suggested. In this review, we summarize the biology of CCL17, its regulation and its potential contribution to the pathogenesis of various preclinical models. Reference is made, for example, to recent literature indicating a role for CCL17 in the control of pain as part of a granulocyte macrophage–colony-stimulating factor/CCL17 pathway in lymphocyte-independent models and thus not as a T-cell chemokine. The review also discusses the potential for CCL17 to be a biomarker and a therapeutic target in human disorders.

更新日期：2023-03-28

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