Cutine Anabela M, Bach Camila A, Veigas Florencia, Merlo Joaquín P, Laporte Lorena, Manselle Cocco Montana N, Massaro Mora, Sarbia Nicolas, Perrotta Ramiro M, Mahmoud Yamil D, Rabinovich Gabriel A
Instituto de Biología y Medicina Experimental (IBYME), Laboratorios de Inmunopatología, Glicómica Funcional e Inmuno-Oncología Translacional, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), C1428 Buenos Aires, Argentina.
Glycobiology. 2021 Sep 9;31(8):891-907. doi: 10.1093/glycob/cwab007.
The relevance of glycan-binding proteins in immune tolerance and inflammation has been well established, mainly by studies of C-type lectins, siglecs and galectins, both in experimental models and patient samples. Galectins, a family of evolutionarily conserved lectins, are characterized by sequence homology in the carbohydrate-recognition domain, atypical secretion via an endoplasmic reticulum-Golgi-independent pathway and by the ability to recognize β-galactoside-containing saccharides. Galectin-1 (Gal-1), a prototype member of this family, displays mainly anti-inflammatory and immunosuppressive activities, although, similar to many cytokines and growth factors, it may also trigger paradoxical pro-inflammatory effects under certain circumstances. These dual effects could be associated to tissue-, time- or context-dependent regulation of galectin expression and function, including particular pathophysiologic settings and/or environmental conditions influencing the structure of this lectin, as well as the availability of glycosylated ligands in immune cells during the course of inflammatory responses. Here, we discuss the tissue-specific role of Gal-1 as a master regulator of inflammatory responses across different pathophysiologic settings, highlighting its potential role as a therapeutic target. Further studies designed at analyzing the intrinsic and extrinsic pathways that control Gal-1 expression and function in different tissue microenvironments may contribute to delineate tailored therapeutic strategies aimed at positively or negatively modulating this glycan-binding protein in pathologic inflammatory conditions.
聚糖结合蛋白在免疫耐受和炎症中的相关性已得到充分证实，主要是通过在实验模型和患者样本中对C型凝集素、唾液酸结合凝集素和半乳糖凝集素的研究。半乳糖凝集素是一类进化上保守的凝集素，其特征在于碳水化合物识别结构域中的序列同源性、通过内质网-高尔基体非依赖途径的非典型分泌以及识别含β-半乳糖苷糖类的能力。半乳糖凝集素-1（Gal-1）是该家族的原型成员，主要表现出抗炎和免疫抑制活性，尽管与许多细胞因子和生长因子类似，在某些情况下它也可能引发矛盾的促炎作用。这些双重效应可能与半乳糖凝集素表达和功能的组织、时间或背景依赖性调节有关，包括影响该凝集素结构的特定病理生理环境和/或环境条件，以及炎症反应过程中免疫细胞中糖基化配体的可用性。在此，我们讨论Gal-1作为不同病理生理环境中炎症反应的主要调节因子的组织特异性作用，强调其作为治疗靶点的潜在作用。旨在分析控制不同组织微环境中Gal-1表达和功能的内在和外在途径的进一步研究，可能有助于制定针对病理性炎症条件下正向或负向调节这种聚糖结合蛋白的定制治疗策略。
