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应答幅度。特异性受体底物的调节性糖基化可以通过产生或掩蔽内源性凝集素的配体来影响免疫功能。本研究主要针对糖基化信号在免疫生物学中调节免疫应答的作用及其应用进行了研究，主要研究结果如下：1.结肠直肠肿瘤相关的Le^a/Le^B b聚糖是癌细胞系和原发性结肠癌上皮细胞上DC-SIGN的重要配体，DC-SIGN和结肠直肠肿瘤相关Le聚糖之间的糖基化依赖性相互作用强烈增强了LPS诱导的MoDC和LPS-10的抗炎细胞因子IL-6和IL-10分泌。MoDCs与癌细胞共培养的上清明显抑制MoDCs诱导的功能成熟。这些结果表明，DC-SIGN在结合结直肠肿瘤相关的Le^a/Le^B后， 关于我们 聚糖可能干扰TLR介导的信号。巨噬细胞脱唾液酸糖蛋白结合蛋白（Macrophage asialoglycoprotein-binding protein，M-ASGP-BP）是一种Gal/GalNAc特异性凝集素，具有内吞受体的功能。我们发现LPS能够以时间依赖性的方式下调巯基乙酸诱导的大鼠和小鼠腹腔巨噬细胞M-ASGP-BP的mRNA表达，并且M-ASGP-BP的mRNA表达通过LPS介导的涉及NF-κ B激活的TLR 4途径下调. CD 26被鉴定为T淋巴细胞上的一种新的DC-SIGN配体，在抗CD 26和抗DC-SIGN抗体的免疫共沉淀物中也检测到ADA和CD 45，提示DC-SIGN和CD 26-ADA-CD 45复合物簇可能在免疫突触的形成和共刺激信号传导中起重要作用.从新生猪和成年猪血清中分离并鉴定了一种新的磷酸甘露聚糖结合凝集素（PMBL）。猪PMBL通过与磷酸甘露聚糖和甘露聚糖结合触发的凝集素途径在功能上激活补体系统，与MBP不同，其被含甘露糖-6-磷酸或半乳糖的寡糖有效抑制。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