Regulation of T lymphocyte responses by glycosylation signals in immunobiology and application

糖基化信号控制关键的淋巴细胞过程，包括淋巴细胞归巢、胸腺细胞选择和免疫反应幅度。特定受体底物的调节糖基化可以通过产生或掩盖内源性凝集素的配体来影响免疫功能。本研究旨在通过糖基化信号调控免疫应答在免疫生物学和应用方面的研究，取得了以下研究结果。结直肠肿瘤相关的Le^a/Le^b糖链是肿瘤细胞和原发癌结肠上皮细胞DC-SIGN的重要配体，DC-SIGN与结直肠癌相关的Le糖链之间的糖基化相互作用强烈地促进了内毒素诱导的MoDC分泌IL-6和IL-10，而与癌细胞共培养的上清明显抑制了内毒素诱导的MoDC的功能成熟。这些结果表明，DC-SIGN与结直肠癌相关的Le^a/Le^b…结合后更多的多糖，可能会干扰TLR介导的信号。巨噬细胞去唾液酸糖蛋白结合蛋白(M-ASGP-BP)是一种Gal/GalNAc特异性凝集素，具有内吞作用。利用硫代乙醇酸诱导的大鼠和小鼠腹腔巨噬细胞，我们发现内毒素能够以时间依赖的方式下调M-ASGP-BP的mRNA表达，并且M-ASGP-BP的mRNA表达被内毒素介导的涉及核因子-kB激活的TLR4途径下调。CD26是T淋巴细胞上一种新的DC-SIGN配体，在与抗CD26和抗DC-SIGN抗体共沉淀物中也检测到ADA和CD45，提示DC-SIGN和CD26-ADA-CD45复合体在免疫突触的形成和共刺激信号的形成中可能发挥重要作用。从新生和成年猪血清中分离并鉴定了一种新的磷甘露聚糖结合凝集素(PMBL)。猪PMBL通过与磷甘露聚糖和甘露聚糖结合而触发的凝集素途径激活补体系统，与MBP不同，这一途径可被含甘露糖-6-磷酸或半乳糖的寡糖有效地抑制。较少

Glycosylation signals control critical lymphocyte processes, including lymphocyte homing, thymocyte selection, and immune response amplitude. Regulated glycosylation of specific acceptor substrates can affect immune functions by creating or masking ligands for endogenous lectins. This research aimed at the regulation of immune responses through glycosylation signals in immunobiology and application, and the following results were clarified.1. Colorectal tumor-associated Le^a/Le^b glycans are important ligands for DC-SIGN on carcinoma cell lines and primary cancer colon epithelia, and glycosylation-dependent interactions between DC-SIGN and colorectal tumor-associated Le glycans strongly enhanced LPS-induced anti-inflammatory cytokines IL-6 and IL-10 secretion by MoDCs and the LPS-induced functional maturation of MoDCs was strikingly inhibited by supernatants of cocultures with the carcinoma cells. These results suggest that DC-SIGN, upon binding of colorectal tumor-associated Le^a/Le^b … More glycans, may interfere with TLR-mediated signals.2. Macrophage asialoglycoprotein-binding protein(M-ASGP-BP) is a Gal/GalNAc-specific lectin, which functions as an endocytosis receptor. We found that LPS is able to down-regulate the mRNA expression of M-ASGP-BP in a time-dependent manner using thioglycolate-elicited rat and mouse peritoneal macrophages, and the mRNA expression of M-ASGP-BP is down-regulated by the LPS-mediated TLR4 pathway involving NF-kB activation.3. CD26 was identified as a novel DC-SIGN ligand on T lymphocytes, and ADA and CD45 were also detected in the co-immunoprecipitates both with anti-CD26 and anti-DC-SIGN antibodies, suggesting that the cluster of DC-SIGN and CD26-ADA-CD45 complex may play an important role in the formation of the immune synapse and the costimulatory signaling.4. A novel phosphomannan-binding lectin (PMBL) was isolated and characterized from both newborn and adult porcine serum. Porcine PMBL functionally activated the complement system through the lectin pathway triggered by binding with both phosphomannan and mannan, which, unlike MBP, was effectively inhibited by mannose-6-phosphate-or galatose-containing oligosaccharides. Less