Current Understanding of IL-37 in Human Health and Disease.

Current Understanding of IL-37 in Human Health and Disease.
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目前对 IL-37 在人类健康和疾病中的了解。

DOI:
10.3389/fimmu.2021.696605
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发表时间:
2021
影响因子:
7.3
通讯作者:
Tao X
Tao X
中科院分区:
医学2区
文献类型:
--
作者:
Su Z;Tao X

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IL-37是最近发现的IL-1家族中的细胞因子,对炎性疾病、自身免疫性疾病和癌症发挥广泛的保护作用。免疫和非免疫细胞在促炎刺激后产生IL-37前体。在细胞内,半胱天冬酶-1切割并激活IL-37,其成熟形式与Smad 3结合;这种复合物易位到细胞核中,在那里它抑制细胞因子的产生,从而减少炎症。在细胞外,IL-37与IL-18 R α和IL-1 R8(以前称为TIR 8或SIGIRR)形成复合物,通过抑制NF-κB和MAPK以及激活Mer-PTEN-DOK通路来转导抗炎信号。在炎症过程中,IL-37通过调节巨噬细胞极化、脂质代谢、炎性体功能、TSLP合成和miRNA功能,抑制多种促炎细胞因子的表达,有利于抗炎细胞因子的表达。此外,IL-37不仅调节先天性和获得性免疫,而且改善衰老相关的免疫衰老。此外,IL-37对肿瘤血管生成、转移和进展具有抑制作用。最后,IL-37可能具有减少过度炎症的潜在能力,因为它在炎性疾病、自身免疫性疾病和癌症患者中异常表达,因此,它可以用作不同类型疾病的标志物。因此,本文综述了IL-37在人类健康和疾病中的作用的最新观点,并讨论了IL-37作为炎症性疾病、自身免疫性疾病和癌症的治疗靶点和生物标志物的潜力。
IL-37 is a recently discovered cytokine in the IL-1 family exerting broad protective effects on inflammatory diseases, autoimmune diseases, and cancer. Immune and non-immune cells produce the IL-37 precursor upon pro-inflammatory stimuli. Intracellularly, caspase-1 cleaves and activates IL-37, and its mature form binds to Smad3; this complex translocates into the nucleus where it suppresses cytokine production, consequently reducing inflammation. Extracellularly, IL-37 forms a complex with IL-18Rα and IL-1R8 (formerly TIR8 or SIGIRR) that transduces anti-inflammatory signals by the suppression of NF-κB and MAPK and the activation of Mer-PTEN-DOK pathways. During inflammation, IL-37 suppresses the expression of several pro-inflammatory cytokine in favor to the expression of the anti-inflammatory ones by the regulation of macrophage polarization, lipid metabolism, inflammasome function, TSLP synthesis and miRNAs function. Moreover, IL-37 not only regulates the innate and acquired immunity, but also improves aging-associated immunosenescence. Furthermore, IL-37 exerts an inhibitory effect on tumor angiogenesis and metastasis, and progression. Finally, IL-37 may have a potential ability to reduce excessive inflammation since it is aberrantly expressed in patients with inflammatory diseases, autoimmune diseases, and cancer, thus, it may be used as a marker for different types of diseases. Therefore, this review provides an updated view of the role of IL-37 in human health and disease, and discusses the potential of IL-37 as a therapeutic target and biomarker in inflammatory diseases, autoimmune diseases, and cancer.
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