Cytokine-induced modulation of T cell antigen receptor signaling

杀伤T淋巴细胞是自身免疫性疾病的重要介质，但它们必须在诱导组织损伤之前被激活。在大多数自身免疫性疾病的情况下，仍然不知道是什么触发了潜在的自我反应性T细胞破坏健康组织的能力。目前的证据表明，适当的遗传和环境因素必须以某种方式相互作用，以刺激潜在的自我毁灭性杀伤T细胞。这些环境因素之一被认为是微生物病原体。某些病毒和细菌被认为与自身免疫性疾病的发生、进展和恶化有关。然而，涉及一种自身免疫性疾病的病原体可能非常多样化，并且没有共同点。这意味着病原体本身可能不会直接诱发自身免疫性疾病。因此，我们推测，某些因素，同样受到不同的病原体可能是各种病原体相关的自身免疫性疾病的基础。我们已经观察到，一组由微生物诱导的炎症因子，称为细胞因子，可以以非常规的方式激活杀伤T细胞，并增加它们对人体自身组织的反应性。在这个项目中，我们研究了细胞因子如何异常地增强杀伤T细胞识别和杀死健康组织的能力，从而导致自身免疫性疾病。

Killer T lymphocytes are important mediators of autoimmune diseases, but they must be activated before they can induce tissue damage. In most cases of autoimmune diseases, it remains unknown what triggers the ability of potentially self-reactive T cells to damage healthy tissues. Current evidence suggests that appropriate genetic and environmental factors must interact in certain ways to stimulate potentially self-destructive killer T cells. One of these environmental factors is thought to be microbial pathogens. Certain viruses and bacteria are believed to be associated with the initiation, progression and exacerbation of autoimmune diseases. However, pathogens implicated in one single autoimmune disease may be very diverse and have nothing in common. This implies that pathogens per se may not directly induce autoimmune diseases. Therefore, we speculate that certain factors that are similarly affected by different pathogens might underlie various pathogen-associated autoimmune diseases. We have observed that one group of inflammatory factors induced by microbes, called cytokines, can activate killer T cells in an unconventional manner and increase their reactivity to body's own tissues. In this project, we investigate how cytokines aberrantly boost the ability of killer T cells to recognize and kill healthy tissues leading to autoimmune diseases.