Neutrophil proteases degrade autoepitopes of NET-associated proteins

Neutrophils can form neutrophil extracellular traps (NETs) to capture microbes and facilitate their clearance. NETs consist of decondensed chromatin decorated with anti-microbial proteins. Here, we describe the effect of neutrophil proteases on the protein content of NETs. We show that the neutrophil serine proteases degrade several neutrophil proteins associated with NETs. Interestingly, the anti-bacterial proteins associated with NETs, such as myeloperoxidase, calgranulin B and neutrophil elastase (NE), seem to be less susceptible to proteolytic degradation than other NET proteins, such as actin and MNDA. NETs have been proposed to play a role in autoimmune reactions. Our data demonstrate that a large number of the autoepitopes of NET proteins that are recognized by autoantibodies produced by systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients are also removed by the proteases. In conclusion, neutrophil serine proteases have a major impact on the NET proteome and the proteolytic changes of NET-associated proteins may counteract autoimmune reactions to NET components.     

Trade-offs between acquired and innate immune defenses in humans

Immune defenses provide resistance against infectious disease that is critical to survival. But immune defenses are costly, and limited resources allocated to immunity are not available for other physiological or developmental processes. We propose a framework for explaining variation in patterns of investment in two important subsystems of anti-pathogen defense: innate (non-specific) and acquired (specific) immunity. The developmental costs of acquired immunity are high, but the costs of maintenance and activation are relatively low. Innate immunity imposes lower upfront developmental costs, but higher operating costs. Innate defenses are mobilized quickly and are effective against novel pathogens. Acquired responses are less effective against novel exposures, but more effective against secondary exposures due to immunological memory. Based on their distinct profiles of costs and effectiveness, we propose that the balance of investment in innate versus acquired immunity is variable, and that this balance is optimized in response to local ecological conditions early in development. Nutritional abundance, high pathogen exposure and low signals of extrinsic mortality risk during sensitive periods of immune development should all favor relatively higher levels of investment in acquired immunity. Undernutrition, low pathogen exposure, and high mortality risk should favor innate immune defenses. The hypothesis provides a framework for organizing prior empirical research on the impact of developmental environments on innate and acquired immunity, and suggests promising directions for future research in human ecological immunology.     

亚慢性硝酸钇暴露对雌性大鼠学习记忆能力的影响

目的：观察稀土化合物硝酸钇[Y（NO₃）₃]亚慢性（90 d）暴露对大鼠学习记忆能力的影响，并探究其可能的机制，为全面评估稀土元素钇的健康风险提供科学依据。方法：选用刚离乳（PND21）SD雌性大鼠，根据质量随机分为4组，分别为对照组（ddH₂O），Y（NO₃）₃低剂量组[10 mg/（kg·d）]、中剂量组[40 mg/（kg·d）]和高剂量组[160 mg/（kg·d）]，每组15只。连续灌胃受试物90 d后进行旷场实验、高架十字迷宫实验、转棒实验、Morris水迷宫实验。水迷宫检测后，每组取5只雌鼠心脏原位灌注，进行脑组织病理学检查。每组剩余10只雌鼠摘取脑组织，紫外分光光度计检测雌鼠大脑皮质和海马中谷氨酸（Glu）的含量；Western blot检测海马组织中N-甲基-D-天冬氨酸（NMDA）受体蛋白表达情况。结果：与对照组相比，硝酸钇90 d暴露后，转棒实验中160 mg/（kg·d）剂量组大鼠在棒时间、在棒圈数、掉落速度明显升高（P<0.05）。在Morris水迷宫定位航向实验第4天时，40、160 mg/（kg·d）剂量组大鼠逃避潜伏期明显降低（P<0.05）；Morris水迷宫空间探索实验中，40 mg/（kg·d）剂量组大鼠穿越平台次数、目标象限游泳时间明显增加（P<0.05）；160 mg/（kg·d）剂量组穿越平台次数、进入目标象限次数、目标象限游泳时间明显增加（P<0.05）；160 mg/（kg·d）剂量组大鼠东北、东南、西南象限的逃避潜伏期明显低于西北象限的逃避潜伏期（P<0.05）。160 mg/（kg·d）剂量组大鼠海马中Glu含量和NMDA受体NR1含量均明显低于对照组（P<0.05）。40和160 mg/（kg·d）剂量组大鼠海马中NMDA受体NR2A含量明显低于对照组（P<0.05）。结论：硝酸钇亚慢性（90 d）暴露可以引起雌性大鼠空间学习记忆能力增强；硝酸钇可能通过降低海马组织神经元细胞外Glu含量，抑制NMDA受体激活，增强雌性大鼠的空间学习记忆能力。     

Pathophysiology and management of sensitive skin: position paper from the special interest group on sensitive skin of the International Forum for the Study of Itch (IFSI)

The special interest group on sensitive skin of the International Forum for the Study of Itch previously defined sensitive skin as a syndrome defined by the occurrence of unpleasant sensations (stinging, burning, pain, pruritus and tingling sensations) in response to stimuli that normally should not provoke such sensations. This additional paper focuses on the pathophysiology and the management of sensitive skin. Sensitive skin is not an immunological disorder but is related to alterations of the skin nervous system. Skin barrier abnormalities are frequently associated, but there is no cause and direct relationship. Further studies are needed to better understand the pathophysiology of sensitive skin – as well as the inducing factors. Avoidance of possible triggering factors and the use of well-tolerated cosmetics, especially those containing inhibitors of unpleasant sensations, might be suggested for patients with sensitive skin. The role of psychosocial factors, such as stress or negative expectations, might be relevant for subgroups of patients. To date, there is no clinical trial supporting the use of topical or systemic drugs in sensitive skin. The published data are not sufficient to reach a consensus on sensitive skin management. In general, patients with sensitive skin require a personalized approach, taking into account various biomedical, neural and psychosocial factors affecting sensitive skin.