Role of Melanocyte Defect in Smyth Line Vitiligo

描述(申请人提供)：白癜风是一种常见的获得性色素减退疾病，其特征是表皮黑素细胞丢失。 尽管白癜风的发病机制仍不清楚，但有证据表明 提示在许多情况下，白癜风是一种自身免疫性疾病，黑素细胞 丢失是免疫反应的结果。突变的Smyth系鸡 是公认的自身免疫性白癜风动物模型。这条线上的鸡 在6到14岁之间，羽毛和脉络膜组织中的黑色素产生细胞(黑素细胞)在出生后出现自发的白癜风样的丧失。 只有几周大。像许多自身免疫性疾病一样，SL白癜风是一个多因素的疾病 疾病，涉及先天的黑素细胞缺陷，免疫系统的一个组成部分， 和环境因素。 对SL黑素细胞中表现出的基本缺陷的研究描述 在孵化过程中存在一个合格的色素系统。在可见的迹象出现之前 白癜风，在SL黑素细胞中检测到的最早异常是 含有色素膜延伸的不规则形状的黑素小体， 过度黑化和黑素小体的选择性自噬。这些 在体内和体内，异常的过程先于SL黑素细胞的退化 在体外，但不足以引起白癜风的表达 正常运作的免疫系统。进行性功能障碍的潜在机制 SL的退化，最终，免疫识别和破坏 人们对黑素细胞知之甚少。 这项建议的目的是研究地方和地方政府 白斑性SL黑素细胞的内环境有助于和/或 导致黑素细胞退化和自身免疫的发展 白癜风。具体地说，我们建议研究氧化应激的作用， 抗氧化力、炎症介质和免疫功能的研究 黑素细胞在体内和体外黑素细胞退化/存活中的作用 这些研究将使用羽毛组织和黑素细胞培养进行。 来自对白癜风发展高度敏感的SL鸡， 易患白癜风的亲本BL鸡，但 很少表达白癜风，而对白癜风有抵抗力的LBL鸡。这个 从这些研究中获得的关于潜在的 SL黑素细胞固有易变性和易感性的机制 自身免疫破坏。可能为治疗和预防艾滋病开辟新的场所 这种紊乱。

DESCRIPTION (provided by applicant): Vitiligo is a common acquired hypopigmentary disorder characterized by a loss of epidermal melanocytes. Although the pathogenesis of vitiligo is still poorly understood, evidence suggests that in many cases vitiligo is an autoimmune disorder and melanocyte loss is the result of an immunological response. The mutant Smyth line chicken is an accepted animal model for autoimmune vitiligo. Chickens from this line develop a spontaneous, vitiligo-like, postnatal loss of melanin producing pigment cells (melanocytes) in feather and choroidal tissue between 6 and 14 weeks of age. Like many autoimmune diseases, SL vitiligo is a multifactorial disorder, involving an inherent melanocyte defect, an immune system component, and an environmental component. Studies examining the basic defect manifested within the SL melanocyte describe the presence of a competent pigment system at hatch. Prior to visible signs of vitiligo, the earliest abnormality detected within SL melanocytes are irregularly shaped melanosomes containing pigmented membrane extensions, hyperactive melanization, and selective autophagocytosis of melanosomes. These aberrant processes precede the degeneration of SL melanocytes in vivo and in vitro but are not sufficient to cause the expression of vitiligo without a functioning immune system. Mechanisms underlying the dysfunction, progressive degeneration, and eventually, immune recognition and destruction of SL melanocytes are poorly understood. It is the goal of this proposal to study the mechanism by which the local and internal environment of the vitiliginous SL melanocyte contributes to and/or results in the degeneration of melanocytes and the development of autoimmune vitiligo. Specifically, we propose to investigate the role of oxidative stress, antioxidant capacity, inflammatory mediators and immunofunctional activities of melanocytes in the degeneration/survival of melanocytes in vivo and in vitro. These studies will be carried out using feather tissue and melanocyte cultures from SL chickens that are highly susceptible to the development of vitiligo, parental BL chickens that are susceptible to the development of vitiligo but rarely express vitiligo, and LBL chickens that are vitiligo resistant. The knowledge that will be gained from these studies regarding the underlying mechanism of the SL melanocyte's inherent susceptibility for degeneration and autoimmune destruction. may open up new venues for treatment and prevention of this disorder.