Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil.
National Institute of Science and Technology on Neuroimmunomodulation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil.
Front Endocrinol (Lausanne). 2024 Oct 17;15:1200935. doi: 10.3389/fendo.2024.1200935. eCollection 2024.
Galectin-3 is an endogenous lectin which binds mainly to β-galactosides on the cell surface and extracellular matrix (ECM) glycoproteins. In the thymus, this lectin is constitutively expressed, being involved in thymocyte adhesion, migration, and death. Galectin-3 has been related to type 1 diabetes, an autoimmune disease characterized by pancreatic β-cell destruction mediated by autoreactive T lymphocytes. Non-obese diabetic (NOD) mice represent a suitable model to study type 1 diabetes, as they develop the disease like humans. We previously described important thymic alterations in these animals such as the development of giant perivascular spaces (PVS), characterized by the retention of T and B cells, intermingled with an ECM network, and associated with a defect in the expression of the fibronectin receptor VLA-5 and reduced sphingosine-1-phosphate receptor expression on developing thymocytes. In order to investigate galectin-3 expression in thymic microenvironmental cells and verify its interaction with cells and ECM molecules in PVS, we performed immunofluorescence following colocalization analysis in the thymic parenchyma of pre-diabetic NOD mice by confocal microscopy. In addition, thymocyte migration assays were performed to evaluate the effect of galectin-3 on NOD thymocyte migration. Herein, we showed a significant enhancement of colocalization with cortical and medullary thymic epithelial cells in NOD mice, as compared to controls. In the giant PVS of these animals, we observed a heterogeneous distribution of galectin-3, predominantly found in clusters of B lymphocytes and dendritic cells. Functionally, NOD thymocyte migratory response towards galectin-3 was impaired and a similar decrease was seen in transendothelial thymocyte migration. Taken together, our data provide the histological and functional background for a potential defective thymocyte migration involving galectin-3, thus placing this molecule as a further player in the intrathymic disturbances observed in pre-diabetic NOD mice.
半乳糖凝集素-3 是一种内源性凝集素，主要与细胞表面和细胞外基质 (ECM) 糖蛋白上的 β-半乳糖苷结合。在胸腺中，这种凝集素持续表达，参与胸腺细胞的黏附、迁移和死亡。半乳糖凝集素-3 与 1 型糖尿病有关，1 型糖尿病是一种自身免疫性疾病，其特征是自身反应性 T 淋巴细胞介导的胰腺 β 细胞破坏。非肥胖型糖尿病 (NOD) 小鼠是研究 1 型糖尿病的合适模型，因为它们像人类一样患这种疾病。我们之前描述了这些动物的重要胸腺改变，例如巨血管周围间隙 (PVS) 的发展，其特征是 T 和 B 细胞的保留，与 ECM 网络交织在一起，并与纤维连接蛋白受体 VLA-5 的表达缺陷和发育中的胸腺细胞上的鞘氨醇-1-磷酸受体表达减少有关。为了研究半乳糖凝集素-3 在胸腺微环境细胞中的表达，并验证其与 PVS 中细胞和 ECM 分子的相互作用，我们通过共聚焦显微镜在糖尿病前期 NOD 小鼠的胸腺实质中进行了免疫荧光，随后进行了共定位分析。此外，还进行了胸腺细胞迁移实验，以评估半乳糖凝集素-3 对 NOD 胸腺细胞迁移的影响。在此，我们显示与对照组相比，NOD 小鼠的皮质和髓质胸腺上皮细胞的共定位显著增强。在这些动物的巨大 PVS 中，我们观察到半乳糖凝集素-3 的异质性分布，主要存在于 B 淋巴细胞和树突状细胞的簇中。功能上，NOD 胸腺细胞对半乳糖凝集素-3 的迁移反应受损，跨内皮胸腺细胞迁移也出现类似减少。综上所述，我们的数据为潜在的缺陷性胸腺细胞迁移提供了组织学和功能背景，涉及半乳糖凝集素-3，从而将该分子作为糖尿病前期 NOD 小鼠中观察到的胸腺内紊乱的另一个参与者。
