Kodali Sreedevi, Ding Wanhong, Huang Jing, Seiffert Kristina, Wagner John A, Granstein Richard D
Department of Dermatology, Joan and Sanford I. Weill Medical College of Cornell University, 525 East 68th Street, New York, NY 10021, USA.
J Immunol. 2004 Nov 15;173(10):6082-8. doi: 10.4049/jimmunol.173.10.6082.
Epidermal nerves lie in close proximity to Langerhans cells (LC) and are capable of releasing peptides that modulate LC function, including calcitonin gene-related peptide and pituitary adenylate cyclase-activating polypeptide. The neuropeptide vasoactive intestinal peptide (VIP) has also been found in cutaneous nerves and mRNA, for the VIP receptor vasoactive intestinal peptide receptor type 1, and vasoactive intestinal peptide receptor type 2 have been found in murine LC and the LC-like cell line XS106. We examined the effects of VIP on LC function and cutaneous immunity. VIP inhibited elicitation of a delayed-type hypersensitivity response in previously immunized mice by epidermal cells enriched for LC content pulsed with Ag in vitro. VIP also inhibited the ability of unseparated epidermal cells to present Ag to a T cell clone and hybridoma and the ability of highly enriched LCs to present to the T cell clone. Inhibition of presentation to the hybridoma was observed with an antigenic peptide that does not require processing, suggesting that VIP is active at a step independent of Ag processing. To elucidate the mechanism(s) by which VIP may mediate these effects, we determined the effects of VIP on LC cytokine production using the XS106 cell line as a surrogate for LC. VIP augmented the production of the IL-10 in LPS-stimulated XS106 cells while down-regulating IL-12 and IL-1beta production. Thus, VIP, like pituitary adenylate cyclase-activating polypeptide and calcitonin gene-related peptide, down-regulates LC function and the associated immune response.
表皮神经与朗格汉斯细胞（LC）紧密相邻，能够释放调节LC功能的肽类，包括降钙素基因相关肽和垂体腺苷酸环化酶激活多肽。神经肽血管活性肠肽（VIP）也已在皮肤神经中发现，并且在小鼠LC和LC样细胞系XS106中发现了VIP受体1型血管活性肠肽受体和2型血管活性肠肽受体的mRNA。我们研究了VIP对LC功能和皮肤免疫的影响。VIP抑制了先前免疫的小鼠中由体外经抗原脉冲处理的富含LC的表皮细胞引发的迟发型超敏反应。VIP还抑制了未分离的表皮细胞将抗原呈递给T细胞克隆和杂交瘤的能力，以及高度富集的LC将抗原呈递给T细胞克隆的能力。对于不需要加工的抗原肽，观察到对杂交瘤的呈递受到抑制，这表明VIP在独立于抗原加工的步骤中起作用。为了阐明VIP介导这些作用可能的机制，我们使用XS106细胞系作为LC的替代物，确定了VIP对LC细胞因子产生的影响。VIP增强了LPS刺激的XS106细胞中IL-10的产生，同时下调了IL-12和IL-1β的产生。因此，与垂体腺苷酸环化酶激活多肽和降钙素基因相关肽一样，VIP下调LC功能和相关的免疫反应。
