Ilic Natasa, Bojic-Trbojevic Zanka, Lundström-Stadelmann Britta, Cujic Danica, Mitic Ivana, Gruden-Movsesijan Alisa
University of Belgrade, Institute for the Application of Nuclear Energy, Banatska 31b, 11080 Belgrade, Serbia.
Institute of Parasitology, Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Länggassstrasse 122, 3012 Bern, Switzerland.
EXCLI J. 2022 Jun 3;21:793-813. doi: 10.17179/excli2022-4954. eCollection 2022.
The immunomodulatory potential of muscle larvae excretory-secretory products (ES L1) has been well documented on dendritic cells (DCs) and in animal models of autoimmune diseases. ES L1 products possess the potential to induce tolerogenic DCs and consequently trigger regulatory mechanisms that maintain immune homeostasis. The use of ES L1 as a potential treatment for various inflammatory disorders proved to be beneficial in animal models, although the precise immunomodulatory factors have not yet been identified. This study aimed at the isolation and characterization of ES L1 components that possess galectin family member properties. Galectin-1-like proteins (TsGal-1-like) were isolated from ES L1 based on the assumption of the existence of a lactose-specific carbohydrate-recognition domain and were recognized by anti-galectin-1 antibodies in Western blot. This TsGal-1-like isolate, similar to galectin-1, induced DCs with tolerogenic properties and hence, the capacity to polarize T cell response towards a regulatory type. This was reflected by a significantly increased percentage of CD4CD25Foxp3 regulatory T cells and significantly increased expression of IL-10 and TGF-β within this cell population. Proteomic analysis of TsGal-1-like isolate by mass spectrometry identified nineteen proteins, seven with annotated function after blast analysis against a database for and the UniProt database. To our surprise, none of the identified proteins possesses homology with known galectin family members. Nevertheless, the isolated components of ES L1 possess certain galectin-1 properties, such as specific lactose binding and the potential to elicit a regulatory immune response, so it would be worth further investigating the structure of sugar binding within isolated proteins and its biological significance.
肌肉幼虫排泄分泌产物（ES L1）的免疫调节潜力在树突状细胞（DCs）和自身免疫性疾病动物模型中已有充分记录。ES L1产物具有诱导耐受性DCs的潜力，从而触发维持免疫稳态的调节机制。尽管尚未确定确切的免疫调节因子，但在动物模型中，使用ES L1作为各种炎症性疾病的潜在治疗方法已被证明是有益的。本研究旨在分离和鉴定具有半乳糖凝集素家族成员特性的ES L1成分。基于乳糖特异性碳水化合物识别结构域存在的假设，从ES L1中分离出类半乳糖凝集素-1蛋白（TsGal-1-like），并在蛋白质印迹中被抗半乳糖凝集素-1抗体识别。这种TsGal-1-like分离物与半乳糖凝集素-1相似，可诱导具有耐受性的DCs，因此具有将T细胞反应极化至调节型的能力。这表现为CD4CD25Foxp3调节性T细胞的百分比显著增加，以及该细胞群体中IL-10和TGF-β的表达显著增加。通过质谱对TsGal-1-like分离物进行蛋白质组学分析，鉴定出19种蛋白质，其中7种在针对 和UniProt数据库进行blast分析后具有注释功能。令我们惊讶的是，鉴定出的蛋白质均与已知的半乳糖凝集素家族成员无同源性。然而，ES L1的分离成分具有某些半乳糖凝集素-1特性，如特异性乳糖结合和引发调节性免疫反应的潜力，因此进一步研究分离蛋白质中糖结合的结构及其生物学意义将是值得的。
