Department of Immunology and Inflammation, IRCCS Humanitas Research Hospital, Rozzano, Italy.
Department of Biomedical Science, Humanitas University, Pieve Emanuele, Italy.
Front Immunol. 2022 Feb 8;13:804641. doi: 10.3389/fimmu.2022.804641. eCollection 2022.
Interleukin-1 (IL-1) is a primary cytokine of innate immunity and inflammation. IL-1 belongs to a complex family including ligands with agonist activity, receptor antagonists, and an anti-inflammatory cytokine. The receptors for these ligands, the IL-1 Receptor (IL-1R) family, include signaling receptor complexes, decoy receptors, and negative regulators. Agonists and regulatory molecules co-evolved, suggesting the evolutionary relevance of a tight control of inflammatory responses, which ensures a balance between amplification of innate immunity and uncontrolled inflammation. IL-1 family members interact with innate immunity cells promoting innate immunity, as well as with innate and adaptive lymphoid cells, contributing to their differentiation and functional polarization and plasticity. Here we will review the properties of two key regulatory receptors of the IL-1 system, IL-1R2, the first decoy receptor identified, and IL-1R8, a pleiotropic regulator of different IL-1 family members and co-receptor for IL-37, the anti-inflammatory member of the IL-1 family. Their complex impact in pathology, ranging from infections and inflammatory responses, to cancer and neurologic disorders, as well as clinical implications and potential therapeutic exploitation will be presented.
白细胞介素-1（IL-1）是先天免疫和炎症的主要细胞因子。IL-1 属于一个复杂的家族，包括具有激动剂活性的配体、受体拮抗剂和抗炎细胞因子。这些配体的受体，即白细胞介素-1 受体（IL-1R）家族，包括信号转导受体复合物、诱饵受体和负调节剂。激动剂和调节分子共同进化，表明炎症反应的严格控制具有进化相关性，这确保了先天免疫的放大和失控性炎症之间的平衡。IL-1 家族成员与先天免疫细胞相互作用，促进先天免疫，以及与先天和适应性淋巴样细胞相互作用，有助于它们的分化和功能极化和可塑性。在这里，我们将回顾 IL-1 系统的两个关键调节受体，即第一个鉴定出的诱饵受体 IL-1R2 和多效调节因子 IL-1R8 的特性，IL-1R8 是不同的 IL-1 家族成员的调节因子，也是 IL-1 家族抗炎成员 IL-37 的共受体。它们在病理学中的复杂影响，从感染和炎症反应到癌症和神经紊乱，以及临床意义和潜在的治疗利用，将被呈现。
