Dendritic cell maturation in active immunotherapy strategies

Dendritic cells (DCs) loaded with tumour antigen have become the centrepiece of clinical trials testing active immunotherapy strategies. Important variables include the source of DCs, the choice of antigens, the method of antigen loading and the route and timing of administration. Recently, the requirement for and the method of, DC maturation have been receiving particular attention. This is due to observations from in vitro studies and animal models demonstrating that mature DCs induce more potent antigen-specific T-cells responses than immature DCs. Furthermore, preliminary observations in human studies suggest that immature DCs might actually downregulate antigen-specific T-cell responses but mature DCs may augment them. Current studies are addressing how to define DC maturation, whether the variety of methods for maturation result in DCs with similar T-cell stimulatory capacity, how to maintain the maturational status and whether maturation in vitro before immunisation, or in vivo, after immunisation, results in better DC function.     

Cardiovascular biomarkers in patients with psoriasis

Psoriasis is a systemic inflammatory disease of the skin with associated comorbidity. Severe forms of psoriasis are associated with increased mortality, which might be due to cardiovascular (CV) comorbidity. In this study, we investigated in 79 patients with psoriasis compared to 80 healthy volunteers different biomarkers that play a role in vascular disease and inflammation, such as C‐reactive protein (CRP), human soluble CD40 ligand (sCD40L), oxidized low‐density lipoprotein (ox‐LDL), human matrix Gla protein (MGP) and fetuin‐A. Our results showed that CRP (P < 0.0001), sCD40L (P < 0.0001) and MGP (P < 0.0001) were increased in the patient cohort. Fetuin‐A showed decreased serum levels in patients with psoriasis (P < 0.0001), whereas ox‐LDL did not show any significant difference. In multivariate analyses controlling for sex, age and BMI, these findings were confirmed. Thus, CV biomarkers are altered in patients with psoriasis. If the decrease in fetuin‐A as well as the increase in sCD40L can be proven in further studies, these biomarkers may help to characterize a subgroup of patients who are at risk to develop CVD and/or monitor the effect of therapeutic antipsoriatic strategies on concomitant diseases. This knowledge may be useful in the management of high‐need patients with psoriasis.     

不同强度电针治疗对血管性痴呆大鼠学习记忆功能及海马CA1区β淀粉样蛋白1-40表达的影响

目的观测不同强度电针治疗对血管性痴呆大鼠学习记忆功能及海马CA1区β淀粉样蛋白1-40(Aβ1-40)表达的影响,寻求最佳电针治疗强度。方法共纳入60只雄性SPF级SD大鼠,采用随机数字表法随机选取8只大鼠为假手术组,其余大鼠采用改良的四血管阻断(4-VO)法复制VD模型,将造模成功的大鼠(24只)按随机数字表法完全随机分为模型组、1 m A电针组(频率2/15 Hz,强度1 m A,留针时间20 min)、3 m A电针组(频率2/15 Hz,强度3 m A,留针时间20 min),每组8只。电针组针刺"百会"、"大椎"穴,1次/d,连续治疗10 d,休息2 d为1个疗程。2个疗程后,采用Morris水迷宫试验检测各组大鼠学习记忆能力,运用荧光定量聚合酶链反应法检测大鼠海马CA1区Aβ1-40 m RNA表达水平。结果假手术组、模型组、1 m A电针组、3 m A电针组大鼠Morris水迷宫试验第2~5天平均逃避潜伏期分别为(46.8±1.9)、(40.6±2.3)、(24.6±1.5)、(19.4±1.2)s;(56.3±3.5)、(51.2±2.6)、(45.9±2.1)、(40.8±1.4)s;(52.7±1.5)、(46.0±2.3)、(31.3±1.2)、(27.7±1.6)s;(50.8±3.9)、(41.5±2.1)、(29.0±1.1)、(25.6±1.3)s;首次跨越原平台时间分别为(23.3±1.6)、(53.9±1.3)、(30.2±1.4)、(28.1±0.8)s,120 s内跨越原平台次数分别为(9.4±0.9)、(2.6±0.5)、(6.4±0.7)、(7.2±0.9)次;CA1区中Aβ1-40 mRNA表达水平分别为(17.3±1.1)、(40.7±1.1)、(24.0±1.7)、(22.4±1.8),组间差异均有统计学意义(F值分别为195.88、861.605、103.876、380.609,均P0.01);1 m A、3 m A电针组大鼠平均逃避潜伏期、首次跨越原平台时间较模型组明显缩短,120 s内跨越原平台次数较模型组明显增加,CA1区中Aβ1-40 mRNA表达水平较模型组明显降低,且3 m A电针组均明显优于1 m A电针组,差异均有统计学意义(均P0.05)。结论电针治疗可改善VD大鼠学习记忆能力并降低海马CA1区Aβ1-4 0 mRNA表达水平,3 m A电针效果优于1 m A电针。     

Complement inhibition in pre-clinical models of periodontitis and prospects for clinical application

Periodontitis is a dysbiotic inflammatory disease leading to the destruction of the tooth-supporting tissues. Current therapies are not always effective and this prevalent oral disease continues to be a significant health and economic burden. Early clinical studies have associated periodontitis with elevated complement activity. Consistently, subsequent genetic and pharmacological studies in rodents have implicated the central complement component C3 and downstream signaling pathways in periodontal host-microbe interactions that promote dysbiosis and inflammatory bone loss. This review discusses these mechanistic advances and moreover focuses on the compstatin family of C3 inhibitors as a novel approach to treat periodontitis. In this regard, local application of the current lead analog Cp40 was recently shown to block both inducible and naturally occurring periodontitis in non-human primates. These promising results from non-human primate studies and the parallel development of Cp40 for clinical use highlight the feasibility for developing an adjunctive, C3-targeted therapy for human periodontitis.     

Enhanced immune‐modulatory effects of thalidomide and dexamethasone co‐treatment on T cell subsets

Thalidomide (TM) has been reported to have anti‐cancer and anti‐inflammatory properties, and dexamethasone (DX) is known to reduce inflammation and inhibit production of inflammatory cytokines. Many studies have reported that combinatorial therapy with TM and DX is clinically used to treat multiple myeloma and lupus nephritis, but the mechanism responsible for its effects has not been elucidated. In this study, we determined that TM and DX co‐treatment had an enhanced immune‐modulatory effect on T cells through regulating the expression of co‐stimulatory molecules. Splenic naive T cells from C57BL/6 mice were sort‐purified and cultured for CD4⁺ T cell proliferation and regulatory T (Treg) cell conversion in the presence of TM and/or DX. Following incubation with the drugs, cells were collected and OX40, 4‐1BB, and glucocorticoid‐induced tumour necrosis factor receptor‐related protein (GITR) expression was quantified by flow cytometry. TM (1 or 10 μm ) decreased CD4⁺ T cell proliferation in a dose‐dependent manner, whereas TM/DX (0·1 or 1 nm ) co‐treatment further decreased proliferation. Treg cell populations were preserved following drug treatment. Furthermore, expression of co‐stimulatory molecules decreased upon TM/DX co‐treatment in effector T (Teff) cells and was preserved in Treg cells. Splenic CD4⁺ T cells isolated from TM‐ and DX‐treated mice exhibited the same patterns of Teff and Treg cell populations as observed in vitro. Considering the selective effect of TM on different T cell subsets, we suggest that TM may play an immunomodulatory role and that TM/DX combinatorial treatment could further enhance these immunomodulatory effects by regulating GITR, OX40, and 4‐1BB expression in CD4⁺ T cells.