Cutaneous denervation of psoriasiform mouse skin improves acanthosis and inflammation in a sensory neuropeptide-dependent manner.
Cutaneous denervation of psoriasiform mouse skin improves acanthosis and inflammation in a sensory neuropeptide-dependent manner.
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DOI：
10.1038/jid.2011.60
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发表时间：
2011-07
影响因子：
6.5
通讯作者：
Ward, Nicole L.
中科院分区：
文献类型：
--
作者：
Ostrowski, Stephen M.;Belkadi, Abdelmadjid;Loyd, Candace M.;Diaconu, Doina;Ward, Nicole L.
神经系统参与银屑病发病机制的证据包括银屑病皮肤中神经纤维数量和神经肽的增加，以及详细描述神经损伤后自发斑块缓解的报告。使用KC-Tie 2银屑病样小鼠模型，我们研究了神经损伤导致炎症性皮肤病缓解的机制。手术切断支配KC-Tie 2动物背部皮肤的皮神经，并在去神经后1天开始，CD 11 c+细胞数量减少40%，随后在7天棘皮病改善30%，到10天CD 4 + T细胞数量减少30%。去神经支配的KC-Tie 2皮肤中SP信号的恢复阻止了CD 11 c+和CD 4+细胞的减少，但对棘皮病没有影响; CGRP信号的恢复逆转了棘皮病的改善，并阻止了去神经支配介导的CD 4+细胞的减少。在神经支配条件下，KC-Tie 2动物中SP的小分子抑制导致与手术去神经后观察到的皮肤CD 11 c+和CD 4+细胞数量相似的减少;而CGRP的小分子抑制导致CD 4+细胞数量和棘皮症显著减少。这些数据表明，感觉神经源性肽介导银屑病样树突状细胞和T细胞浸润和棘层形成，并引入靶向神经-免疫细胞/角质形成细胞相互作用作为潜在的银屑病治疗性治疗策略。
Nervous system involvement in psoriasis pathogenesis is supported by increases in nerve fiber numbers and neuropeptides in psoriatic skin and by reports detailing spontaneous plaque remission following nerve injury. Using the KC-Tie2 psoriasisform mouse model, we investigated the mechanisms by which nerve injury leads to inflammatory skin disease remission. Cutaneous nerves innervating dorsal skin of KC-Tie2 animals were surgically axotomized and beginning 1d following denervation, CD11c+ cell numbers decreased by 40% followed by a 30% improvement in acanthosis at 7d and a 30% decrease in CD4+ T cell numbers by 10d. Restoration of SP signaling in denervated KC-Tie2 skin prevented decreases in CD11c+ and CD4+ cells but had no affect on acanthosis; restoration of CGRP signaling reversed the improvement in acanthosis and prevented denervated-mediated decreases in CD4+ cells. Under innervated conditions, small molecule inhibition of SP in KC-Tie2 animals resulted in similar decreases to those observed following surgical denervation for cutaneous CD11c+ and CD4+ cell numbers; whereas small molecule inhibition of CGRP resulted in significant reductions in CD4+ cell numbers and acanthosis. These data demonstrate that sensory nerve-derived peptides mediate psoriasiform dendritic cell and T cell infiltration and acanthosis and introduce targeting nerve-immunocyte/keratinocyte interactions as potential psoriasis therapeutic treatment strategies.
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影响因子：
6
作者：
Joachim, Ricarda Alcira;Handjiski, Bori;Arck, Petra Clara
通讯作者：
Arck, Petra Clara
影响因子：
6.5
作者：
Ding, Wanhong;Wagner, John A.;Granstein, Richard D.
通讯作者：
Granstein, Richard D.
影响因子：
3.6
作者：
FARBER, EM;LANIGAN, SW;BOER, J
通讯作者：
BOER, J
影响因子：
3.6
作者：
Legat, FJ;Jaiani, LT;Ansel, JC
通讯作者：
Ansel, JC
DOI：
10.1073/pnas.0409569102
发表时间：
2005-02-08
影响因子：
11.1
作者：
Chamian, F;Lowes, MA;Krueger, JG
通讯作者：
Krueger, JG