Role of Melanocyte Defect in Smyth Line Vitiligo

描述（由申请人提供）：白癜风是一种常见的后天性 以表皮黑素细胞的丧失为特征的色素减退症。 虽然白癜风的发病机制仍然知之甚少，证据 表明在许多情况下白癜风是一种自身免疫性疾病， 丧失是免疫反应的结果。突变的史密斯线鸡 是公认的自身免疫性白癜风动物模型。这条线上的鸡 产生自发的、白癜风样的、产后黑色素产生的损失 羽毛和脉络膜组织中的色素细胞（黑色素细胞）在6至14岁之间 周的年龄。像许多自身免疫性疾病一样，SL白癜风是一种多因素 疾病，涉及固有的黑素细胞缺陷，免疫系统成分， 和环境因素。 对SL黑素细胞内表现出的基本缺陷进行了研究， 孵化时存在一个合格的色素系统。在出现明显的 白癜风，最早检测到的异常SL黑色素细胞是 含有色素膜延伸的不规则形状的黑素体， 过度活跃的黑化和黑素体的选择性自噬作用。这些 异常过程先于SL黑素细胞在体内和体内的变性， 但不足以引起白癜风的表达， 免疫系统功能功能障碍的潜在机制，进行性 退化，并最终，免疫识别和破坏SL 对黑素细胞了解甚少。 本建议的目的是研究地方和地方政府之间 白癜风SL黑素细胞的内部环境有助于和/或 导致黑素细胞的退化和自身免疫性疾病的发展。 白癜风具体来说，我们建议研究氧化应激的作用， 抗氧化能力，炎症介质和免疫功能活性 在体内和体外黑素细胞的变性/存活中， 这些研究将使用羽毛组织和黑素细胞培养物进行 从对白癜风发展高度易感的SL鸡， 父母的BL鸡，容易发展白癜风，但 很少表达白癜风，LBL鸡是白癜风抵抗。的 从这些研究中获得的关于潜在的 SL黑素细胞固有的变性易感性的机制， 自身免疫性破坏可能会开辟新的治疗和预防场所， 这种混乱。

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.