Immune cell trafficking to the islets during type 1 diabetes

Inhibition of immune cell trafficking to the pancreatic islets during type 1 diabetes (T1D) has therapeutic potential, since targeting of T cell and B cell trafficking has been clinically effective in other autoimmune diseases. Trafficking to the islets is characterized by redundancy in adhesion molecule and chemokine usage, which has not enabled effective targeting to date. Additionally, cognate antigen is not consistently required for T cell entry into the islets throughout the progression of disease. However, myeloid cells are required to enable T cell and B cell entry into the islets, and may serve as a convergence point in the pathways controlling this process. In this review we describe current knowledge of the factors that mediate immune cell trafficking to pancreatic islets during T1D progression.     

Novel Risk Factors for Progression of Diabetic and Nondiabetic CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

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Decreased circulating CXCR3 + CCR9+T helper cells are associated with elevated levels of their ligands CXCL10 and CCL25 in the salivary gland of patients with Sjögren’s syndrome to facilitate their concerted migration

CCR9 + T helper (Th) cells can induce Sjögren-like symptoms in mice and both CCR9 + Th cells and their ligand CCL25 are increased in the salivary glands of primary Sjögren's syndrome (pSS) patients. Increased circulating CCR9 + Th cells are present in pSS patients. CCR9 + Th cells are hyperresponsive to IL-7, secrete high levels of IFN-γ, IL-21, IL-17 and IL-4 and potently stimulate B cells in both patients and healthy individuals. Our aim was to study co-expression of chemokine receptors on CCR9 + Th cells and whether in pSS this might differentially affect CCR9 + Th cell frequencies. Frequencies of circulating CCR9 + and CCR9- Th cells co-expressing CXCR3, CCR4, CCR6 and CCR10 were studied in pSS patients and healthy controls. CCL25, CXCL10, CCL17, CCL20 and CCL27 mRNA and protein expression of salivary gland tissue of pSS and non-Sjögren's sicca (non-SS) patients was assessed. Chemotaxis assays were performed to study migration induced by CXCL10 and CCL25. Higher expression of CXCR3, CCR4 and CCR6 but not CCR10 was observed on CCR9 + Th cells as compared to cells lacking CCR9. Decreased frequencies of circulating memory CCR9 + CXCR3+ Th cells were found in pSS patients, which was most pronounced in the effector memory subset. Increased salivary gland CCL25 and CXCL10 expression significantly correlated and both ligands functioned synergistically based on in vitro induced chemotaxis. Decreased memory CXCR3 + CCR9+ Th cells in blood of pSS patients may be due to a concerted action of overexpressed ligands at the site of inflammation in the salivary glands facilitating their preferential migration and positioning in the lymphocytic infiltrates.     

The potential role for infections in the pathogenesis of autoimmune Addison’s disease

Autoimmune Addison’s disease (AAD), or primary adrenocortical insufficiency, is a classical organ-specific autoimmune disease with 160 years of history. AAD is remarkably homogeneous with one major dominant self-antigen, the cytochrome P450 21-hydroxylase enzyme, which is targeted by both autoantibodies and autoreactive T cells. Like most autoimmune diseases, AAD is thought to be caused by an unfortunate combination of genetic and environmental factors. While the number of genetic associations with AAD is increasing, almost nothing is known about environmental factors. A major environmental factor commonly proposed for autoimmune diseases, based partly on experimental and clinical data and partly on shared pathways between anti-viral immunity and autoimmunity, is viral infections. However, there are few reports associating viral infections to AAD, and it has proved difficult to establish which immunological processes that could link any viral infection with the initiation or progression of AAD. In this review, we will summarize the current knowledge on the underlying mechanisms of AAD and take a closer look on the potential involvement of viruses.     

Cooperation between Constitutive and Inducible Chemokines Enables T Cell Engraftment and Immune Attack in Solid Tumors

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牙周炎和趋化因子的研究新进展

趋化因子(chemokines)是一类一级结构相似,对白细胞具有化学趋化作用等多种生物学效应的小分子蛋白,在机体的防御和炎症反应等方面起着重要的调节作用.近年来许多研究发现,趋化因子在牙周炎的免疫发病机制中发挥着重要作用.深入研究趋化因子和牙周炎的关系,对牙周炎的预防、诊断、治疗以及治疗后疗效监测有重要意义.     

Differential in situ distribution of interleukin-8, monocyte chemoattractant protein-1 and Rantes in human chronic periapical granuloma

In situ distribution of three prototype chemokines interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1 and Rantes was determined in chronic human periapical granulomas by immunohistochemistry using monoclonal antibodies. IL-8 was found primarily in the cytoplasm of the Malassez epithelial cells. MCP-1 immunoreactivity was confined to the endothelial cells that lined small venules. Each of the three investigated chemokines, including Rantes, exhibited a characteristic binding pattern to the extracellular matrix of the lesion. The observed chemokines may play a role in establishing the cellular composition of chronic apical periodontitis, thus augmenting the intensity of local inflammation and tissue damage.     

红藤合剂灌肠联合输卵管通液术治疗输卵管阻塞性不孕的临床疗效及对盆腔局部微环境的影响

目的 评价红藤合剂灌肠联合输卵管通液术治疗对输卵管阻塞性不孕的临床疗效及对盆腔局部微环境的影响。方法 选取2019年5月—2020年9月海南省中医院140例输卵管阻塞性不孕患者作为研究对象,按照随机数字表法分为对照组和观察组,每组70例。对照组采用输卵管通液术治疗;观察组在对照组治疗的基础上给予红藤合剂灌肠。3个月后行子宫输卵管造影检查,比较两组输卵管再通情况;随访12个月,比较两组妊娠情况和复发情况;对所有患者进行治疗前后中医症候和局部体征评分;比较两组子宫内膜厚度和子宫内膜类型、子宫内膜动脉阻力指数（RI）、搏动指数（PI）及血管化血流指数（VFI）;检测治疗前后宫腔液白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、转化生长因子-β₁（TGF-β₁）及结缔组织生长因子（CTGF）水平;检测治疗前后月经血趋化因子1（CXCL1）、趋化因子13（CXCL13）、IL-6及TNF-α水平;对所有患者行安全性评价。结果 治疗后,观察组输卵管再通率为76.19%（48/63）,高于对照组的58.06%（36/62）（P <0.05）。12个月随访期间,观察组妊娠率为70.83%（34/48）,高于对照组的44.44%（16/36）（P <0.05）;观察组复发率为12.50%（6/48）,低于对照组的30.56%（11/36）（P <0.05）。治疗后两组患者中医症候和局部体征评分较治疗前均降低（P <0.05）,且观察组评分低于对照组（P <0.05）。治疗后两组患者子宫内膜厚度、A型子宫内膜类型比例及VFI增加（P <0.05）,RI和PI较治疗前降低（P <0.05）,且观察组VFI高于对照组,RI和PI低于对照组（P <0.05）。治疗后两组患者宫腔液IL-6、TNF-α、TGF-β₁及CTGF水平较治疗前降低（P <0.05）,且观察组低于对照组（P <0.05）。治疗后两组患者月经血CXCL1、CXCL13、IL-6及TNF-α水平较治疗前降低（P <0.05）,且观察组低于对照组（P <0.05）。研究期间未发现与使用红藤合剂灌肠相关的不良反应。结论 红藤合剂灌肠联合输卵管通液术治疗输卵管阻塞性不孕可减轻临床症状,改善局部微循环和局部微环境,提高输卵管再通率和临床妊娠率,并降低复发率,临床使用安全。