Coordination Funds

我们的免疫系统保护我们免受病原体的侵害，并清除可能导致恶性肿瘤的异常细胞。当以最高效率去除威胁同时避免对宿主的附带组织损伤时，实现最佳的免疫稳态。越来越多的科学证据表明，这种免疫平衡在男女之间是不同的。研究表明，妇女对病原体产生更强的免疫反应，从而更快地控制或清除感染。妇女对疫苗接种也会产生更强的免疫力，并对某些恶性肿瘤表现出更强的免疫反应。然而，增强女性的免疫反应是有代价的，包括加重的组织损伤、持续的炎症和显著更高的自身免疫性疾病发病率。这些性别特异性差异不仅限于成年人，因为男孩在生命早期感染的风险已经增加，而女孩在青春期患特应性疾病的风险更大。尽管女性和男性之间感染性和自身免疫性疾病的临床表现存在这些明确的差异，但尚未系统地研究潜在的生物学机制。RU 5068“免疫力的性别差异”的总体目标是系统地研究针对自身和外来免疫力的性别特异性差异的潜在机制，重点关注女性和男性之间存在患病率和表现差异的人类疾病。RU 5068将评估常见生物学途径导致性别差异的主要假设，并将确定（i）性类固醇激素和（ii）X染色体基因调节导致免疫性别差异的免疫学途径的机制。我们的RU汇集了基础和临床科学家，他们在自身免疫，传染病和恶性肿瘤领域的特定研究各自领域的领导者，并对免疫的性别特异性差异有很强的研究重点。RU 5068的优势之一是在评估对外源或自身免疫力的不同模型中研究性激素和X染色体基因对免疫力的影响。拟议的工作计划将结合联合收割机使用人类样本来研究免疫学差异，并结合小鼠模型来确定潜在的机制和测试干预措施。了解免疫力性别差异的机制将为考虑受影响个体性别的传染性和免疫介导疾病的新治疗策略铺平道路。

Our immune system defends us from pathogens and removes abnormal cells that potentially lead to malignancies. Optimal immunological homeostasis is achieved when the threat is removed with the highest efficiency whilst avoiding collateral tissue damage for the host. Increasing scientific evidence suggests that this immunological balance is different between women and men. It has been shown that women mount stronger immune responses against pathogens, leading to more rapid control or clearance of infections. Women also develop stronger immunity in response to vaccinations, and exhibit stronger immune responses against some malignancies. Enhanced immune responsiveness in females, however, comes at a cost, including aggravated tissue damage, persistent inflammation and significantly higher incidences of autoimmune diseases. These sex-specific differences are not restricted to adults, as already boys have an increased risk for infections early in life, while girls develop a greater risk for atopic diseases around puberty. Despite these well-established differences in clinical manifestations of infectious and autoimmune diseases between females and males, the underlying biological mechanisms have not been systematically examined. The overall goal of the RU 5068 “sex differences in immunity” is to systematically investigate mechanisms underlying sex-specific differences in immunity against self and foreign, focusing on human diseases for which differences in prevalence and manifestations exist between women and men. The RU 5068 will assess the principal hypothesis that common biological pathways are responsible for sex-based differences, and will determine the mechanisms by which (i) sex steroid hormones and (ii) X chromosomal genes modulate immunological pathways responsible for sex differences in immunity. Our RU brings together basic and clinician scientists that are leaders in their respective fields of specific research in the areas of autoimmunity, infectious diseases and malignancies, and have a strong research focus on sex-specific differences in immunity. One of the strengths of the RU 5068 is that consequences of sex hormones and X chromosomal genes on immunity are investigated in different models assessing immunity to foreign or self. The proposed work program will combine use of human samples to investigate immunological differences, and mouse models to identify underlying mechanisms and to test interventions. The understanding of the mechanisms underlying sex differences in immunity will pave the way for novel treatment strategies for infectious and immune-mediated diseases that take the sex of the affected individual into account.