TGF-β: 20 years and counting

The history of transforming growth factor-beta (TGF-β) as a bifunctional agent in the immune system is briefly described. The importance of cellular context in understanding the role of TGF-β in regulating immune response is emphasized.     

蛹虫草缓解新型冠状病毒感染研究进展

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的COVID-19在全球范围内大流行,危害了人类健康和公共安全,随着对SARS-CoV-2的结构、功能和致病过程的了解,越来越多的潜在药物被开发。蛹虫草(Cordyceps militaris)是我国传统的药用真菌,具有显著的抗病毒作用,虫草素作为蛹虫草的主要活性成分能够与SARS-CoV-2刺突蛋白、主蛋白酶(Mpro)相结合,抑制病毒RNA依赖的RNA聚合酶(RDRP)活性,阻断SARS-CoV-2在机体内复制。蛹虫草还具有提升机体免疫力、修复受损组织的作用。本文概述虫草素抗SARS-CoV-2的机制和蛹虫草其他相关药理作用,以期为蛹虫草用于新型冠状病毒感染的辅助治疗提供参考。     

Vasoactive Intestinal Peptide (VIP) Inhibits Substrate Adherence Capacity of Rat Peritoneal Macrophages by a Mechanism That Involves cAMP

In this study, vasoactive intestinal peptide (VIP) is shown to inhibit substrate adherence capacity of rat peritoneal macrophages. The inhibitory response occurred in the 0.1-1, 000 nM range of VIP concentrations and it was a time-dependent process. At 15 min, half maximal inhibition (ICw) was obtained at 0.37 ± 0.26 nM and maximal inhibition (53.8%) at 10^-6 M VIP. The inhibitory effect of VIP was correlated with the stimulation by this peptide of cyclic AMP (cAMP) production in rat peritoneal macrophages. Moreover, agents that inhibited VIP-stimulated cAMP production, such as the VIP-antagonist [4-Cl-D-Phe₆ Leu₁₇]-VIP and somatostatin, also decreased the inhibitory effect of VIP on substrate adherence capacity of macrophages. On the contrary, the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) and the lipid-soluble derivative of cAMP N⁶ 2'-O-dibutyryl cAMP (Bu-cAMP) inhibited the adherence of macrophages to substrate and potentiated the inhibitory action of VIP. These results demonstrate that VIP inhibits substrate adherence capacity of rat peritoneal macrophages by a mechanism that involves cAMP, and show, for the first time, an action of VIP on the function of peritoneal macrophages.     

TGF-β in infections and infectious diseases

Since it was first described as having the ability to inhibit macrophage activation, transforming growth factor-beta (TGF-β) has been analyzed for its role in regulating immune responses to a variety of pathogens, including viruses, bacteria, yeast, and protozoa. Most of the studies have involved organisms that infect macrophages, and this discussion will attempt to highlight these findings. Perhaps the most work has been performed with protozoan pathogens, including Trypanosoma cruzi and a variety of Leishmania species, so the discussion will begin with these organisms. Other studies have focused on mycobacteria and viruses, including human immunodeficiency virus, so these areas will also be emphasized in the discussion. For the most part, investigators have reported that TGF-β has, as expected, a negative influence on host responses and a beneficial effect on the survival and growth of intracellular pathogens. However, other studies have found that TGF-β may have a positive or beneficial effect in some models of infection. This review will attempt to highlight studies and conclusions on the roles of TGF-β in infection.     

脐带间充质干细胞治疗儿童重型免疫性血小板减少症的探索性研究

目的探讨脐带间充质干细胞（UC-MSC）输注治疗儿童重型免疫性血小板减少症（s ITP）的疗效及安全性。方法采用UC-MSC治疗儿童s ITP 3例。发病年龄为3个月至4岁,初治时血小板计数为（1-7）×10^9/L,3例均为s ITP,均出现严重出血,激素及免疫抑制剂无效或依赖。后给予2-3次（1次/周）静脉输注非血缘UC-MSC,输注细胞量为（1-2）×10^6/kg。输注后密切监测血象及肝肾功能等各项指标,观察疗效及不良反应。结果随访时间15-45个月,3例在输注细胞后渐显效：第1例在输注细胞后20 d血小板达到65×10^9/L,随访4个月,血小板均维持在1×10^11/L以上;第2例在输注细胞后41 d血小板达105×10^9/L,之后血小板一直维持正常;第3例在输注第2次细胞后血小板渐上升至2×10^11/L以上。输注过程中1例出现面色发红,1例出现血压升高,随访至今无明显不良反应。结论 UC-MSC对儿童重型ITP有一定的疗效,能提高儿童的生活质量;有必要扩大病例数,进一步研究UC-MSC治疗儿童ITP的疗效及机制。     

DC—SIGN固有免疫调节及其表达调控机制研究进展

DC—SIGN（DC—specificICAM-3-grabbingnonintegrin,CD209）系C型凝集素家族主要成员,具有模式识别受体和介导细胞黏附功能。DC-SIGN可通过分子中凝集素糖识别域,识别多种病原体的外源性和机体内源性抗原以及细胞表面黏附分子（ICAM-2,3）中甘露糖或岩藻糖的糖基团,并对话协调Toll样受体等,介导树突状细胞（DC）等参与病原体或肿瘤细胞的免疫逃逸;也可调节DC黏附迁移并在炎症启动中激活初始T细胞免疫应答。因而,作为天然免疫分子介导基础,DC．SIGN在DC参与的感染性和炎症性疾病等的正负免疫调节中发挥了关键作用。目前有关DC．SIGN免疫调节效应涉及的信号转导以及分子表达调控机制尚未完全阐明,就相关进展作一综述。     

耗竭性T细胞在肿瘤中的作用

耗竭性T细胞(exhausted T cells)是一群效应功能减弱,持续表达抑制性受体的T细胞,在肿瘤中表现为T细胞功能缺陷状态,主要特征为一系列抑制性受体表达增加及细胞因子分泌减少。耗竭性T细胞主要通过细胞表面的抑制性分子,细胞因子和免疫调节细胞类型改变等参与肿瘤免疫负调控,从而引起肿瘤免疫逃逸。而T细胞耗竭状态并非不可逆转,应用相应单克隆抗体靶向免疫调控点可以有效逆转耗竭性T细胞,恢复机体抗肿瘤免疫反应,提高肿瘤控制率。因此,通过逆转肿瘤患者体内的耗竭性T细胞可能是肿瘤免疫治疗的新途径之一。     

精氨酸加压素对大鼠抗体产生和淋巴细胞增殖的上调作用

大鼠侧脑室注射１００ｎｇ精氨酸加压素（ＡＶＰ）,用ＥＬＩＳＡ法检测血中对鸡卵白 白抗原产生的ＩｇＧ抗体水平。结果显示,ＩｇＧ水平高于对照,而ＡＶＰ的Ｖ１受体阻断剂ＤＰＡＶＰ则可阻断此作用;ｉｃｖ８００ｎｇＡＶＰ,大鼠的ＳＲＢＣ溶血素 水平高于对照;ｉｃｖ１００ｎｇ、８００ｎｇＡＶＰ２ｈ后,脾淋巴细胞对ＭＴＴ产生的颜色反应均比对照增加,而ＤＰＡＶＰ可阻断之;ｉｃｖ８００ＡＶＰ２ｈ后,脾淋巴细胞对ＭＴ     

急性低氧下去甲肾上腺素对大鼠淋巴细胞转化的调节作用

本研究以模拟高原低氧方法,观察低氧作用于大鼠细胞免疫功能以及去甲肾上腺素对免疫作用的调节机制。实验结果：与对照相比,７ｋｍ急性低氧２４ｈ淋巴细胞转化下降４１％（Ｐ〈０．０１）;５ｋｍ低氧暴露时间为７ｄ,２０ｄ时,低氧抑制淋巴细胞转化,分别下降３４％和６０％（Ｐ〈０．０１）,侧脑室注入５ｎｍｏｌ／Ｌ ＮＥ,淋巴细胞转化比对照下降２９％（Ｐ〈０．０１）,７ｋｍ１０ｈ低氧暴露时,侧脑室注入酚妥拉明２５μ