• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

皮肤钙/钙调蛋白依赖性蛋白激酶 II-γ 阳性交感神经分泌去甲肾上腺素决定银屑病。

Cutaneous Calcium/Calmodulin-Dependent Protein Kinase II-γ-Positive Sympathetic Nerves Secreting Norepinephrine Dictate Psoriasis.

机构信息

Department of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China.

Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, Hefei, 230032, China.

出版信息

Adv Sci (Weinh). 2024 Jun;11(23):e2306772. doi: 10.1002/advs.202306772. Epub 2024 Mar 28.

DOI:10.1002/advs.202306772
PMID:38544478
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11187923/
Abstract

Cutaneous sympathetic nerve is a crucial part of neuropsychiatric factors contributing to skin immune response, but its role in the psoriasis pathogenesis remains unclear. It is found that cutaneous calcium/calmodulin-dependent protein kinase II-γ (CAMK2γ), expressed mainly in sympathetic nerves, is activated by stress and imiquimod in mouse skin. Camk2g-deficient mice exhibits attenuated imiquimod-induced psoriasis-like manifestations and skin inflammation. CaMK2γ regulates dermal γδT-cell interleukin-17 production in imiquimod-treated mice, dependent on norepinephrine production following cutaneous sympathetic nerve activation. Adrenoceptor β1, the primary skin norepinephrine receptor, colocalises with γδT cells. CaMK2γ aggravates psoriasiform inflammation via sympathetic nerve-norepinephrine-γδT cell-adrenoceptor β1-nuclear factor-κB and -p38 axis activation. Application of alcaftadine, a small-molecule CaMK2γ inhibitor, relieves imiquimod-induced psoriasis-like manifestations in mice. This study reveals the mechanisms of sympathetic-nervous-system regulation of γδT-cell interleukin-17 secretion, and provides insight into neuropsychiatric factors dictating psoriasis pathogenesis and new potential targets for clinical psoriasis treatment.

摘要

皮肤交感神经是导致皮肤免疫反应的神经精神因素的重要组成部分，但它在银屑病发病机制中的作用仍不清楚。研究发现，主要表达于交感神经中的钙/钙调蛋白依赖性蛋白激酶 II-γ（CAMK2γ）可被应激和咪喹莫特激活。钙调蛋白激酶 2γ（CAMK2γ）缺陷型小鼠表现出伊匹莫德诱导的银屑病样表现和皮肤炎症减轻。在咪喹莫特处理的小鼠中，CaMK2γ 调节真皮 γδT 细胞白细胞介素-17 的产生，这依赖于皮肤交感神经激活后去甲肾上腺素的产生。肾上腺素能受体 β1 是皮肤去甲肾上腺素的主要受体，与 γδT 细胞共定位。CaMK2γ 通过交感神经-去甲肾上腺素-γδT 细胞-肾上腺素能受体 β1-核因子-κB 和 -p38 轴的激活加重银屑病样炎症。小分子 CaMK2γ 抑制剂 alcaftadine 的应用可缓解小鼠的咪喹莫特诱导的银屑病样表现。本研究揭示了交感神经系统调节 γδT 细胞白细胞介素-17 分泌的机制，并深入了解了决定银屑病发病机制的神经精神因素和临床银屑病治疗的新潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5e4/11187923/98404575bd8b/ADVS-11-2306772-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5e4/11187923/e97424933541/ADVS-11-2306772-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5e4/11187923/d551cefb483e/ADVS-11-2306772-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5e4/11187923/63dbac1863ca/ADVS-11-2306772-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5e4/11187923/e7b63ba6b998/ADVS-11-2306772-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5e4/11187923/20fc987c705b/ADVS-11-2306772-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5e4/11187923/d58108bed7c5/ADVS-11-2306772-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5e4/11187923/98404575bd8b/ADVS-11-2306772-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5e4/11187923/e97424933541/ADVS-11-2306772-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5e4/11187923/d551cefb483e/ADVS-11-2306772-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5e4/11187923/63dbac1863ca/ADVS-11-2306772-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5e4/11187923/e7b63ba6b998/ADVS-11-2306772-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5e4/11187923/20fc987c705b/ADVS-11-2306772-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5e4/11187923/d58108bed7c5/ADVS-11-2306772-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5e4/11187923/98404575bd8b/ADVS-11-2306772-g006.jpg

相似文献

1
Cutaneous Calcium/Calmodulin-Dependent Protein Kinase II-γ-Positive Sympathetic Nerves Secreting Norepinephrine Dictate Psoriasis.皮肤钙/钙调蛋白依赖性蛋白激酶 II-γ 阳性交感神经分泌去甲肾上腺素决定银屑病。
Adv Sci (Weinh). 2024 Jun;11(23):e2306772. doi: 10.1002/advs.202306772. Epub 2024 Mar 28.
2
Hyperforin Ameliorates Imiquimod-Induced Psoriasis-Like Murine Skin Inflammation by Modulating IL-17A-Producing γδ T Cells.贯叶金丝桃素通过调节产生白介素-17A 的 γδ T 细胞改善咪喹莫特诱导的银屑病样小鼠皮肤炎症。
Front Immunol. 2021 May 5;12:635076. doi: 10.3389/fimmu.2021.635076. eCollection 2021.
3
NF-κB1 Contributes to Imiquimod-Induced Psoriasis-Like Skin Inflammation by Inducing Vγ4Vδ4γδT17 Cells.NF-κB1 通过诱导 Vγ4Vδ4γδT17 细胞促进咪喹莫特诱导的银屑病样皮肤炎症。
J Invest Dermatol. 2022 Jun;142(6):1639-1649.e5. doi: 10.1016/j.jid.2021.11.004. Epub 2021 Nov 11.
4
Adiponectin-derived pentapeptide ameliorates psoriasiform skin inflammation by suppressing IL-17 production in γδT cells.脂联素衍生五肽通过抑制 γδT 细胞中 IL-17 的产生来改善银屑病样皮肤炎症。
J Dermatol Sci. 2022 Apr;106(1):45-52. doi: 10.1016/j.jdermsci.2022.03.003. Epub 2022 Mar 14.
5
Inhibition of interleukin-2-inducible T-cell kinase causes reduction in imiquimod-induced psoriasiform inflammation through reduction of Th17 cells and enhancement of Treg cells in mice.白细胞介素 2 诱导的 T 细胞激酶抑制可减少 Th17 细胞并增强调节性 T 细胞，从而减轻咪喹莫特诱导的银屑病样炎症反应。
Biochimie. 2020 Dec;179:146-156. doi: 10.1016/j.biochi.2020.09.023. Epub 2020 Sep 29.
6
Nociceptive sensory neurons drive interleukin-23-mediated psoriasiform skin inflammation.伤害感受性感觉神经元驱动白细胞介素-23 介导的银屑病样皮肤炎症。
Nature. 2014 Jun 5;510(7503):157-61. doi: 10.1038/nature13199. Epub 2014 Apr 23.
7
Imiquimod-applied Interleukin-10 deficient mice better reflects severe and persistent psoriasis with systemic inflammatory state.白细胞介素-10 缺陷型咪喹莫特涂抹小鼠更好地反映出具有全身炎症状态的严重和持续的银屑病。
Exp Dermatol. 2018 Jan;27(1):43-49. doi: 10.1111/exd.13403. Epub 2017 Sep 14.
8
C5a/C5aR1 mediates IMQ-induced psoriasiform skin inflammation by promoting IL-17A production from γδ-T cells.C5a/C5aR1 通过促进 γδ-T 细胞产生 IL-17A 介导 IMQ 诱导的银屑病样皮肤炎症。
FASEB J. 2020 Aug;34(8):10590-10604. doi: 10.1096/fj.202000384R. Epub 2020 Jun 18.
9
IL-23/IL-17 immune axis mediates the imiquimod-induced psoriatic inflammation by activating ACT1/TRAF6/TAK1/NF-κB pathway in macrophages and keratinocytes.IL-23/IL-17 免疫轴通过激活巨噬细胞和角质细胞中的 ACT1/TRAF6/TAK1/NF-κB 通路介导咪喹莫特诱导的银屑病炎症。
Kaohsiung J Med Sci. 2023 Aug;39(8):789-800. doi: 10.1002/kjm2.12683. Epub 2023 Apr 26.
10
Depressive-like behaviors in mice with Imiquimod-induced psoriasis.咪喹莫特诱导银屑病样小鼠的抑郁样行为。
Int Immunopharmacol. 2020 Dec;89(Pt B):107057. doi: 10.1016/j.intimp.2020.107057. Epub 2020 Nov 24.

引用本文的文献

1
Skin immune microenvironment in psoriasis: from bench to bedside.银屑病中的皮肤免疫微环境：从实验台到临床
Front Immunol. 2025 Aug 29;16:1643418. doi: 10.3389/fimmu.2025.1643418. eCollection 2025.
2
Impact of serum calcium levels on the occurrence of sepsis and prognosis in hospitalized patients with concomitant psoriasis: a retrospective study based on the MIMIC-IV database.血清钙水平对合并银屑病住院患者脓毒症发生及预后的影响：一项基于MIMIC-IV数据库的回顾性研究
Front Immunol. 2025 Jul 22;16:1621231. doi: 10.3389/fimmu.2025.1621231. eCollection 2025.
3
Molecular Link Between Psoriasis and Depression-Update on Pathophysiology.

本文引用的文献

1
Calcium/calmodulin-dependent protein kinase IV promotes imiquimod-induced psoriatic inflammation via macrophages and keratinocytes in mice.钙/钙调蛋白依赖性蛋白激酶 IV 通过小鼠巨噬细胞和角质形成细胞促进咪喹莫特诱导的银屑病炎症。
Nat Commun. 2022 Jul 22;13(1):4255. doi: 10.1038/s41467-022-31935-8.
2
T-lymphocyte tyrosine hydroxylase regulates T17 T-lymphocytes during repeated social defeat stress.T 淋巴细胞酪氨酸羟化酶在反复社交挫败应激中调节 T17 T 淋巴细胞。
Brain Behav Immun. 2022 Aug;104:18-28. doi: 10.1016/j.bbi.2022.05.007. Epub 2022 May 14.
3
Unmet clinical needs and burden of disease in hidradenitis suppurativa: real-world experience from EU5 and US.
银屑病与抑郁症之间的分子联系——病理生理学最新进展
Int J Mol Sci. 2025 Mar 10;26(6):2467. doi: 10.3390/ijms26062467.
4
Neurogenic inflammation and itch in barrier tissues.屏障组织中的神经源性炎症与瘙痒
Semin Immunol. 2025 Mar;77:101928. doi: 10.1016/j.smim.2024.101928. Epub 2025 Jan 10.
未满足的临床需求和疾病负担：来自欧盟 5 国和美国的真实世界经验。
J Eur Acad Dermatol Venereol. 2022 Sep;36(9):1597-1605. doi: 10.1111/jdv.18163. Epub 2022 May 9.
4
Lidocaine Ameliorates Psoriasis by Obstructing Pathogenic CGRP Signaling‒Mediated Sensory Neuron‒Dendritic Cell Communication.利多卡因通过阻断致病 CGRP 信号介导的感觉神经元-树突状细胞通讯来改善银屑病。
J Invest Dermatol. 2022 Aug;142(8):2173-2183.e6. doi: 10.1016/j.jid.2022.01.002. Epub 2022 Jan 12.
5
Structural mechanism for tyrosine hydroxylase inhibition by dopamine and reactivation by Ser40 phosphorylation.结构机制酪氨酸羟化酶抑制多巴胺和再激活丝氨酸 40 磷酸化。
Nat Commun. 2022 Jan 10;13(1):74. doi: 10.1038/s41467-021-27657-y.
6
Somatosensory and autonomic neuronal regulation of the immune response.躯体感觉和自主神经元对免疫反应的调节。
Nat Rev Neurosci. 2022 Mar;23(3):157-171. doi: 10.1038/s41583-021-00555-4. Epub 2022 Jan 7.
7
Mouse Models of Psoriasis: A Comprehensive Review.银屑病小鼠模型：全面综述。
J Invest Dermatol. 2022 Mar;142(3 Pt B):884-897. doi: 10.1016/j.jid.2021.06.019. Epub 2021 Dec 23.
8
Personal ozone exposure and stress hormones in the hypothalamus-pituitary-adrenal and sympathetic-adrenal-medullary axes.下丘脑-垂体-肾上腺轴和交感-肾上腺髓质轴中的个人臭氧暴露与应激激素
Environ Int. 2022 Jan 15;159:107050. doi: 10.1016/j.envint.2021.107050. Epub 2021 Dec 16.
9
Antigen dominance hierarchies shape TCF1 progenitor CD8 T cell phenotypes in tumors.抗原优势层次结构塑造了肿瘤中 TCF1 祖细胞 CD8 T 细胞的表型。
Cell. 2021 Sep 16;184(19):4996-5014.e26. doi: 10.1016/j.cell.2021.08.020.
10
IL-23/Th17 Axis: A Potential Therapeutic Target of Psoriasis.白细胞介素-23/辅助性T细胞17轴：银屑病的潜在治疗靶点
Curr Drug Res Rev. 2022;14(1):24-36. doi: 10.2174/2589977513666210707114520.