Sundblad Victoria, Morosi Luciano G, Geffner Jorge R, Rabinovich Gabriel A
Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo de Investigaciones Científicas y Técnicas, C1428 Buenos Aires, Argentina.
Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, C1428 Buenos Aires, Argentina.
J Immunol. 2017 Dec 1;199(11):3721-3730. doi: 10.4049/jimmunol.1701172.
Regulatory signals provide negative input to immunological networks promoting resolution of acute and chronic inflammation. Galectin-1 (Gal-1), a member of a family of evolutionarily conserved glycan-binding proteins, displays broad anti-inflammatory and proresolving activities by targeting multiple immune cell types. Within the innate immune compartment, Gal-1 acts as a resolution-associated molecular pattern by counteracting the synthesis of proinflammatory cytokines, inhibiting neutrophil trafficking, targeting eosinophil migration and survival, and suppressing mast cell degranulation. Likewise, this lectin controls T cell and B cell compartments by modulating receptor clustering and signaling, thus serving as a negative-regulatory checkpoint that reprograms cellular activation, differentiation, and survival. In this review, we discuss the central role of Gal-1 in regulatory programs operating during acute inflammation, autoimmune diseases, allergic inflammation, pregnancy, cancer, and infection. Therapeutic strategies aimed at targeting Gal-1-glycan interactions will contribute to overcome cancer immunosuppression and reinforce antimicrobial immunity, whereas stimulation of Gal-1-driven immunoregulatory circuits will help to mitigate exuberant inflammation.
调节信号为促进急性和慢性炎症消退的免疫网络提供负向输入。半乳糖凝集素-1（Gal-1）是进化上保守的聚糖结合蛋白家族的成员，通过靶向多种免疫细胞类型展现出广泛的抗炎和促消退活性。在固有免疫区室中，Gal-1通过对抗促炎细胞因子的合成、抑制中性粒细胞迁移、靶向嗜酸性粒细胞迁移和存活以及抑制肥大细胞脱颗粒，作为一种与消退相关的分子模式发挥作用。同样，这种凝集素通过调节受体聚集和信号传导来控制T细胞和B细胞区室，因此作为一个负调节检查点对细胞活化、分化和存活进行重新编程。在本综述中，我们讨论了Gal-1在急性炎症、自身免疫性疾病、过敏性炎症、妊娠、癌症和感染期间运行的调节程序中的核心作用。旨在靶向Gal-1-聚糖相互作用的治疗策略将有助于克服癌症免疫抑制并增强抗菌免疫，而刺激Gal-1驱动的免疫调节回路将有助于减轻过度炎症。
