Calcitonin gene-related peptide biases Langerhans cells toward Th2-type immunity.
Calcitonin gene-related peptide biases Langerhans cells toward Th2-type immunity.
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DOI：
10.4049/jimmunol.181.9.6020
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发表时间：
2008-11-01
期刊：
影响因子：
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通讯作者：
Granstein RD
中科院分区：
文献类型：
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作者：
Ding W;Stohl LL;Wagner JA;Granstein RD
朗格汉斯细胞（LC）是表皮树突状细胞，在几个实验系统中，其能够呈递Ag以刺激细胞介导的免疫。LC被认为在皮肤免疫应答的启动中起关键作用。此外，将供体T细胞给予具有持续性宿主LC的骨髓嵌合小鼠，而不是LC已被供体细胞替代的小鼠，表现出明显的皮肤移植物抗宿主病，表明LC可引发移植物抗宿主病。然而，转基因小鼠的实验中，从人类langerin的调控元件被用来驱动白喉毒素的表达，导致在没有LC，表明LC可能会下调皮肤免疫。LC与含有神经肽降钙素基因相关肽（CGRP）的神经相关，并且CGRP在几种模型中抑制LC Ag呈递，包括呈递给Th 1克隆。我们现在报告说，CGRP增强LC功能刺激Th 2反应。CGRP暴露增强了LC Ag向Th 2克隆的呈递。在通过LC将鸡卵清蛋白（cOVA）呈递给来自DO11.10 cOVA T细胞受体转基因小鼠的T细胞后，用CGRP预处理导致IL-4产生增加和IFN-γ产生减少。CGRP还抑制刺激产生的Th 1趋化因子CXCL 9和CXCL 10，但诱导产生的Th 2趋化因子CCL 17和CCL 22的树突状细胞系和新鲜获得的LC。这些趋化因子的产生变化与CGRP对这些因子mRNA水平的影响相关。LC暴露于原位神经源性CGRP可能会使它们朝着有利于Th 2型免疫的方向发展。这是作者制作的手稿版本，已被《免疫学杂志》（The JI）接受出版。美国免疫学家协会(AAI)JI的出版商拥有本手稿的版权。这一版本的手稿尚未由联合执行进行复制编辑或编辑校对;因此，它可能与联合执行发表的最后版本（在线和印刷版）不同。AAI（JI）对作者制作的手稿版本或美国国立卫生研究院或任何其他第三方从中衍生的任何版本中的错误或遗漏不承担责任。记录的最终可引用版本可在www.jimmunol.org上找到。
Langerhans cells (LC) are epidermal dendritic cells capable, in several experimental systems, of Ag-presentation for stimulation of cell-mediated immunity. LC have been considered to play a key role in initiation of cutaneous immune responses. Additionally, administration of donor T cells to bone marrow chimeric mice with persistent host LC, but not mice whose LC have been replaced by donor cells, exhibit marked skin graft-versus-host disease, demonstrating that LC can trigger graft-versus-host disease. However, experiments with transgenic mice in which regulatory elements from human langerin were used to drive expression of diphtheria toxin, resulting in absence of LC, suggest that LC may serve to downregulate cutaneous immunity. LC are associated with nerves containing the neuropeptide calcitonin gene-related peptide (CGRP) and CGRP inhibits LC Ag-presentation in several models including presentation to a Th1 clone. We now report that CGRP enhances LC function for stimulation of Th2 responses. CGRP exposure enhanced LC Ag-presentation to a Th2 clone. Upon presentation of chicken ovalbumin (cOVA) by LC to T cells from DO11.10 cOVA T cell receptor transgenic mice,pretreatment with CGRP resulted in increased IL-4 production and decreased IFN-γ production. CGRP also inhibited stimulated production of the Th1 chemokines CXCL9 and CXCL10 but induced production of the Th2 chemokines CCL17 and CCL22 by a dendritic cell line and by freshly-obtained LC. Changes in production of these chemokines correlated with the effect of CGRP on mRNA levels for these factors. Exposure of LC to nerve-derived CGRP in situ may polarize them towards favoring Th2-type immunity. This is an author-produced version of a manuscript accepted for publication in The Journal of Immunology (The JI). The American Association of Immunologists, Inc. (AAI), publisher of The JI,holds the copyright to this manuscript. This version of the manuscript has not yet been copyedited or subjected to editorial proofreading by The JI; hence, it may differ from the final version published in The JI (online and in print). AAI (The JI) is not liable for errors or omissions in this author-produced version of the manuscript or in any version derived from it by the U.S. National Institutes of Health or any other third party. The final, citable version of record can be found at www.jimmunol.org.