Insights into the multifaceted role of interleukin-37 on human immune cell regulation

IF 4.5 3区医学 Q2 IMMUNOLOGY

Clinical immunology Pub Date : 2024-09-20 DOI:10.1016/j.clim.2024.110368

Lisa U. Teufel , Vasiliki Matzaraki , Lukas Folkman , Rob ter Horst , Simone J.C.F.M. Moorlag , Catharina M. Mulders-Manders , Mihai G. Netea , Thomas Krausgruber , Leo A.B. Joosten , Rob J.W. Arts

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Abstract

Autoinflammatory diseases, while having a variety of underlying causes, are mediated by dysfunctional innate immune responses. Therefore, standard treatments target innate cytokines or block their receptors. Despite excellent responses in some patients, first-line treatments fail in others, for reasons which remain to be understood.

We studied the effects of IL-37, an anti-inflammatory cytokine, on immune cells using multi-omics profiling of 325 healthy adults. Our findings show that IL-37 is associated with inflammation control and generally reduced immune cell activity. Further, genetic variants in IL37 are associated with impaired trained immunity, a memory phenotype of innate immune cells contributing to autoinflammation. To underpin the medical potential of IL-37, an explorative cohort of seven autoinflammatory disorders was built. In vitro stimulation experiments argue for recombinant IL-37 as a potential therapy in IL-6-, and IL-22-driven conditions.

Concluding, IL-37 is highlighted as a cytokine with broad anti-inflammatory functions, implicating its potential as therapeutic intervention.

Abstract Image

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洞察白细胞介素-37 对人类免疫细胞调节的多方面作用。

自身炎症性疾病的根本原因多种多样，但都是由功能失调的先天性免疫反应介导的。因此，标准治疗以先天性细胞因子或阻断其受体为目标。尽管一线治疗在一些患者中取得了很好的疗效，但在另一些患者中却失败了，其原因尚不清楚。我们通过对 325 名健康成年人进行多组学分析，研究了抗炎细胞因子 IL-37 对免疫细胞的影响。我们的研究结果表明，IL-37 与炎症控制和免疫细胞活性普遍降低有关。此外，IL37 的遗传变异与训练有素的免疫力受损有关，而训练有素的免疫力是先天性免疫细胞的一种记忆表型，会导致自身炎症。为了证实 IL-37 的医疗潜力，我们建立了一个由七种自身炎症疾病组成的探索性队列。体外刺激实验证明，重组 IL-37 有可能治疗 IL-6 和 IL-22 驱动的疾病。总之，IL-37 是一种具有广泛抗炎功能的细胞因子，具有治疗干预的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical immunology 医学-免疫学

CiteScore

12.30

自引率

1.20%

发文量

212

审稿时长

34 days

期刊介绍： Clinical Immunology publishes original research delving into the molecular and cellular foundations of immunological diseases. Additionally, the journal includes reviews covering timely subjects in basic immunology, along with case reports and letters to the editor.