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。 这项工作是根据最近 朗格汉斯细胞在解剖学上与CGRP相关， 含有表皮轴突，CGRP调节它们的功能， 体外 一系列的实验将检查CGRP与 体外抗原呈递和体内免疫应答。 将对人类皮肤进行形态学研究，以分析 含CGRP轴突与朗格汉斯细胞的解剖关系 在变应性接触性皮炎的演变过程中。 的分布和 将在不同时间点评估CGRP的存在量。 这将 为降钙素基因相关肽在调节皮肤炎症反应中的作用提供了相关证据。 超敏反应 其他实验将证实， CGRP具有生物活性。 为了进一步确定 神经支配皮肤免疫反应，皮肤区域将 在小鼠中进行去神经手术，并且这种去神经皮肤 支持诱导或诱发接触性超敏反应的部位 将被审查。 将进行体外研究，以进一步确定 CGRP的作用。 这些将重点关注CGRP调节的能力 抗原呈递、粘附分子表达和细胞因子释放。 其他实验将试图确定CGRP是否诱导 巨噬细胞或朗格汉斯细胞来提供致耐受性信号，而不是 免疫原性信号。 为了确定外源性给予CGRP是否可以 改变免疫应答，小鼠支持诱导的能力，或 局部或全身接触性超敏反应 将检查CGRP的施用。 本报告提出的研究将 定义了神经系统和 免疫系统. 因此，所获得的结果将提供更大的 了解神经和心理状态如何影响 皮肤的免疫功能 此外，这些发现可能导致 目前未预见到的治疗免疫性疾病的新治疗方法 混乱

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.