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CC 趋化因子受体 4(CCR4)作为一种可能的新治疗靶点。

CC Chemokine Receptor 4 (CCR4) as a Possible New Target for Therapy.

机构信息

Department of Pain Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland.

出版信息

Int J Mol Sci. 2022 Dec 9;23(24):15638. doi: 10.3390/ijms232415638.

Abstract

Chemokines and their receptors participate in many biological processes, including the modulation of neuroimmune interactions. Approximately fifty chemokines are distinguished in humans, which are classified into four subfamilies based on the N-terminal conserved cysteine motifs: CXC, CC, C, and CX3C. Chemokines activate specific receptors localized on the surface of various immune and nervous cells. Approximately twenty chemokine receptors have been identified, and each of these receptors is a seven-transmembrane G-protein coupled receptor. Recent studies provide new evidence that CC chemokine receptor 4 (CCR4) is important in the pathogenesis of many diseases, such as diabetes, multiple sclerosis, asthma, dermatitis, and cancer. This review briefly characterizes CCR4 and its ligands (CCL17, CCL22, and CCL2), and their contributions to immunological and neoplastic diseases. The review notes a significant role of CCR4 in nociceptive transmission, especially in painful neuropathy, which accompanies many diseases. The pharmacological blockade of CCR4 seems beneficial because of its pain-relieving effects and its influence on opioid efficacy. The possibilities of using the CCL2/CCL17/CCL22/CCR4 axis as a target in new therapies for many diseases are also discussed.

摘要

趋化因子及其受体参与许多生物学过程,包括神经免疫相互作用的调节。人类大约有五十种趋化因子,根据 N 端保守半胱氨酸基序分为四个亚家族:CXC、CC、C 和 CX3C。趋化因子激活特定的受体,这些受体位于各种免疫和神经细胞的表面。已经鉴定出大约二十种趋化因子受体,其中每种受体都是一种七跨膜 G 蛋白偶联受体。最近的研究提供了新的证据,表明 C 型趋化因子受体 4(CCR4)在许多疾病的发病机制中很重要,如糖尿病、多发性硬化症、哮喘、皮炎和癌症。本文简要描述了 CCR4 及其配体(CCL17、CCL22 和 CCL2),以及它们在免疫和肿瘤疾病中的作用。本文指出 CCR4 在伤害性传递中具有重要作用,特别是在伴随许多疾病的痛性神经病中。由于 CCR4 具有缓解疼痛的作用及其对阿片类药物疗效的影响,其药理学阻断似乎是有益的。还讨论了将 CCL2/CCL17/CCL22/CCR4 轴作为许多疾病新疗法的靶点的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e471/9779674/2c4458311089/ijms-23-15638-g003.jpg

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