Beyond Negative Regulation: IL-1R8 and IL-1R2 as Novel Immune Checkpoints

IF 3.7 3区 医学 Q2 IMMUNOLOGY
Domenico Supino, Roberto Garuti, Cecilia Garlanda
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引用次数: 0

Abstract

IL-1 family members and their signaling receptors are key drivers of inflammation in sterile or infectious conditions, as well as polarization of the innate and adaptive immunity. Deregulated or excessive activation of the IL-1 system is associated with detrimental inflammatory reactions. Beside signaling receptors, IL-1-family receptors comprise decoy or negative regulatory receptors, which regulate cell activation mediated by IL-1 family ligands. IL-1-family negative regulatory receptors, which include IL-1R8 and IL-1R2, have peculiar structural features and functions essential to the self-regulation of the IL-1 system. IL-1R8 and IL-1R2 emerge as regulatory molecules whose function is context-dependent, spanning from negative regulation of inflammation in infections or conditions of sterile inflammation and cell damage, including cancer-related inflammation, to skewing of myeloid and lymphoid cells, modulation of anti-tumor immunity, and immune checkpoint activity. This review reports new insights into the physio-pathological roles of these two negative regulatory IL-1 family members, emphasizing their mechanisms of action and potential for innovative therapeutic interventions.

Abstract Image

超越负调控:IL-1R8和IL-1R2作为新的免疫检查点
IL-1家族成员及其信号受体是无菌或感染性条件下炎症以及先天和适应性免疫极化的关键驱动因素。IL-1系统的过度激活与有害的炎症反应有关。除信号受体外,IL-1家族受体还包括诱骗受体或负调节受体,它们调节由IL-1家族配体介导的细胞活化。IL-1家族负调节受体,包括IL-1R8和IL-1R2,具有特殊的结构特征和功能,对IL-1系统的自我调节至关重要。IL-1R8和IL-1R2作为调节分子出现,其功能依赖于环境,从感染或无菌炎症和细胞损伤条件下的炎症负调控,包括癌症相关炎症,到骨髓和淋巴细胞的扭曲,抗肿瘤免疫调节和免疫检查点活性。这篇综述报道了这两个负调节IL-1家族成员的生理病理作用的新见解,强调了它们的作用机制和创新治疗干预的潜力。
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来源期刊
CiteScore
8.30
自引率
3.70%
发文量
224
审稿时长
2 months
期刊介绍: The European Journal of Immunology (EJI) is an official journal of EFIS. Established in 1971, EJI continues to serve the needs of the global immunology community covering basic, translational and clinical research, ranging from adaptive and innate immunity through to vaccines and immunotherapy, cancer, autoimmunity, allergy and more. Mechanistic insights and thought-provoking immunological findings are of interest, as are studies using the latest omics technologies. We offer fast track review for competitive situations, including recently scooped papers, format free submission, transparent and fair peer review and more as detailed in our policies.
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