Department of Immunology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.
J Immunol. 2011 Jun 15;186(12):6886-93. doi: 10.4049/jimmunol.1100028. Epub 2011 May 6.
Some cutaneous inflammations are induced by percutaneous exposure to foreign Ags, and many chemical mediators regulate this inflammation process. One of these mediators, calcitonin gene-related peptide (CGRP), is a neuropeptide released from nerve endings in the skin. CGRP binds to its receptors composed of receptor activity-modifying protein 1 and calcitonin receptor-like receptor to modulate immune cell function. We show that CGRP regulates skin inflammation under physiological conditions, using contact hypersensitivity (CHS) models of receptor activity-modifying protein 1-deficient mice. CGRP has different functions in CHS responses mediated by Th1 or Th2 cells; it inhibits Th1-type CHS, such as 2,4,6-trinitrochlorobenzene-induced CHS, but promotes Th2-type CHS, such as FITC-induced CHS. CGRP inhibits the migration of Langerin(+) dermal dendritic cells to the lymph nodes in 2,4,6-trinitrochlorobenzene-induced CHS, and upregulates IL-4 production of T cells in the draining lymph nodes in FITC-CHS. These findings suggest that CGRP regulates several types of CHS reactions under physiological conditions and plays an important role in cutaneous immunity.
某些皮肤炎症是由经皮接触外来抗原引起的，许多化学介质调节着这一炎症过程。其中一种介质，降钙素基因相关肽（CGRP），是一种从皮肤末梢神经释放的神经肽。CGRP 与由活性修饰蛋白 1 和降钙素受体样受体组成的受体结合，调节免疫细胞功能。我们使用活性修饰蛋白 1 缺陷小鼠的接触超敏反应（CHS）模型，表明 CGRP 在生理条件下调节皮肤炎症。CGRP 在由 Th1 或 Th2 细胞介导的 CHS 反应中具有不同的功能；它抑制 Th1 型 CHS，如 2,4,6-三硝基氯苯诱导的 CHS，但促进 Th2 型 CHS，如 FITC 诱导的 CHS。CGRP 抑制 Langerin(+)真皮树突状细胞向 2,4,6-三硝基氯苯诱导的 CHS 中的引流淋巴结迁移，并上调 FITC-CHS 中引流淋巴结中 T 细胞的 IL-4 产生。这些发现表明，CGRP 在生理条件下调节多种类型的 CHS 反应，并在皮肤免疫中发挥重要作用。
