Neuroimmunomodulation within the eye

眼内的神经免疫调节

• 批准号: 7802124
• 负责人: Andrew W Taylor
• 金额: $ 36.2万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7802124
• 关键词: Adverse effects; Antigen Presentation; Autoimmune Diseases; Autoimmune Process; Bacteriophages; Blindness; Cells; Characteristics; Cornea; Eye; Graft Rejection; Hypersensitivity; Immune; Immune response; Immune system; Immunity; Immunosuppression; Immunosuppressive Agents; Inflammation; Inflammatory; Inflammatory Response; MSH receptor; Macrophage Activation; Mediator of activation protein; Natural Immunity; Nervous system structure; Neuroimmunomodulation; Pathway interactions; Physiological; Physiological Adaptation; Reaction; Regulation; Regulatory T-Lymphocyte; Retinal; Role; Sympathectomy; System; Testing; Th1 Cells; Transplanted tissue; Visual; adaptive immunity; immunogenic; immunoregulation; macrophage; pathogen; pigment epithelium-derived factor; prevent; tumor

DESCRIPTION (provided by applicant): The healthy eye possesses a unique physiological and evolutionary adaptation that modifies the expression of immunity. This physiological adaptation is part of ocular immune privilege. The physiological role of immune privilege is to impart upon the eye immune protection that avoids the destructive side effects of immunogenic inflammation. Immunogenic inflammation associated with hypersensitivity reactions can grossly distort the visual axis resulting in blindness. Within the immune privileged ocular microenvironment, there are active mechanisms of immunoregulation and immunosuppression. This ocular system of immunoregulation and immunosuppression not only suppresses immunogenic inflammation, but also actively manipulates immunity to make the immune response itself immunosuppressive. By understanding the mechanism of ocular immunity, it will be possible to induce an immune response that promotes the elimination of pathogens and tumors without the consequences of immunogenic inflammation, prevent or cure ocular and other autoimmune diseases, and induce immunity that promotes acceptance of corneal, retinal, and other tissue transplants. The objectives of this proposal are to identify, characterize, and establish the role of constitutively produced factors that are immunoregulatory and immunosuppressive in the eye. We hypothesize that the such factors suppress the activation of innate and adaptive immunity associated with inflammation, while enhancing or maintaining expression of the characteristics associated with immune regulation or suppression. We will test this hypothesis by demonstrating that the ocular microenvironment promotes the alternative activation and induction of suppressor macrophages, that the ocular microenvironment promotes the induction of effector regulatory T cells, and that the nervous system makes a significant contribution to ocular immunity.

描述（由申请人提供）：健康的眼睛具有独特的生理和进化适应性，可以改变免疫力的表达。这种生理适应是眼部免疫豁免的一部分。免疫赦免的生理作用是赋予眼睛免疫保护，避免免疫原性炎症的破坏性副作用。与超敏反应相关的免疫原性炎症可严重扭曲视轴，导致失明。在免疫赦免的眼部微环境中，存在免疫调节和免疫抑制的活跃机制。这种免疫调节和免疫抑制的眼部系统不仅抑制免疫原性炎症，而且还主动操纵免疫以使免疫应答本身具有免疫抑制性。通过理解眼部免疫的机制，将有可能诱导促进病原体和肿瘤消除而没有免疫原性炎症后果的免疫应答，预防或治愈眼部和其他自身免疫性疾病，并诱导促进接受角膜、视网膜和其他组织移植的免疫。本提案的目的是鉴定、表征和确定组成性产生的免疫调节和免疫抑制因子在眼睛中的作用。我们假设这些因子抑制与炎症相关的先天性和适应性免疫的激活，同时增强或维持与免疫调节或抑制相关的特征的表达。我们将测试这一假设，证明眼微环境促进抑制性巨噬细胞的替代激活和诱导，眼微环境促进效应调节性T细胞的诱导，以及神经系统对眼免疫的重大贡献。