REGULATION OF LANGERHANS CELL FUNCTION BY CGRP

此应用程序的总体目标是评估和定义效果 神经递质和血管扩张剂降钙素基因相关肽 (CGRP)对皮肤免疫功能的影响。这项工作是基于最近的 观察到朗格汉斯细胞在解剖学上与CGRP有关- 含有表皮轴突，CGRP对其功能进行调节 体外培养。一系列实验将检验CGRP与 体外抗原提呈和体内免疫反应性。 将在人类皮肤上进行形态研究，以分析 含CGRP的轴突与朗格汉斯细胞的解剖关系 在过敏性接触性皮炎的演变过程中。分布和分布 CGRP的含量将在不同的时间点进行评估。这将是 为CGRP在皮肤调节中的作用提供相关证据 过敏症。其他实验将证实表皮来源的 降钙素基因相关肽具有生物活性。为了进一步定义 对皮肤免疫反应的神经支配，皮肤区域将 小鼠的手术去神经和这种去神经皮肤的能力 支持诱发或诱发接触性超敏反应的部位 将会被检查。将进行体外研究，以进一步确定 CGRP的作用。这些将集中在CGRP的调节能力上。 抗原提呈、黏附分子表达和细胞因子释放。 其他实验将尝试确定CGRP是否诱导 巨噬细胞或朗格汉斯细胞提供耐受信号，而不是 一种免疫信号。以确定外源性应用CGRP是否可以 改变免疫反应，小鼠支持诱导或 局部或全身后诱发接触性超敏反应 将检查CGRP的管理情况。在此提出的研究将 定义一个重要的神经系统和大脑之间相互作用的场所 免疫系统。因此，所获得的结果将提供更大的 了解神经学和心理状态如何影响 皮肤的免疫功能。此外，这些发现可能会导致 目前无法预见的治疗免疫学疾病的新方法 精神错乱。

The overall goal of this application is to evaluate and define the effects of the neurotransmitter and vasodilator calcitonin gene-related peptide (CGRP) on cutaneous immunologic function. This work is based on recent observations that Langerhans cells are anatomically associated with CGRP- containing epidermal axons and that CGRP regulates their function in vitro. A series of experiments will examine the relevance of CGRP to antigen presentation in vitro and immunologic responsiveness in vivo. Morphologic studies will be performed on human skin to analyze the anatomic relationship between CGRP-containing axons and Langerhans cells during the evolution of allergic contact dermatitis. The distribution and amount of CGRP present will be assessed at various timepoints. This will provide correlative evidence for a role for CGRP in regulating cutaneous hypersensitivity. Other experiments will verify that epidermis-derived CGRP is biologically active. To further define the relevance of innervation to cutaneous immune responses, areas of skin will be denervated surgically in mice and the ability of such denervated skin sites to support the induction or elicitation of contact hypersensitivity will be examined. In vitro studies will be performed to further define the actions of CGRP. These will focus on the ability of CGRP to modulate antigen presentation, adhesion molecule expression, and cytokine release. Other experiments will attempt to determine whether CGRP induces macrophage or Langerhans cells to provide a tolerogenic signal rather than an immunogenic signal. To determine if exogenously administered CGRP can modify immune responses, the ability of mice to support the induction or elicitation of contact hypersensitivity after local or systemic administration of CGRP will be examined. The studies proposed herein will define an important locus of interaction between the nervous system and the immune system. Therefore, the results obtained will provide a greater understanding of how neurologic and psychologic status may influence immune function in the skin. Furthermore, such findings may lead to currently unforeseen new therapeutic approaches to treat immunologic derangements.