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Ash1L ameliorates psoriasis via limiting neuronal activity-dependent release of miR-let-7b
2023-11-01
发表期刊BRITISH JOURNAL OF PHARMACOLOGY (IF:6.8[JCR-2023],7.4[5-Year])
ISSN0007-1188
EISSN1476-5381
发表状态已发表
DOI10.1111/bph.16254
摘要

["Background and PurposePsoriasis is a common autoimmune skin disease that significantly diminishes patients' quality of life. Interactions between primary afferents of the somatosensory system and the cutaneous immune system mediate the pathogenesis of psoriasis. This study aims to elucidate the molecular mechanisms of how primary sensory neurons regulate psoriasis formation.Experimental ApproachSkin and total RNA were extracted from wild-type (WT) and ASH1-like histone lysine methyltransferase (Ash1l+/-) mice in both naive and imiquimod (IMQ)-induced psoriasis models. Immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR) and fluorescence-activated cell sorting (FACS) were then performed. Microfluidic chamber coculture was used to investigate the interaction between somatosensory neurons and bone marrow dendritic cells (BMDCs) ex vivo. Whole-cell patch clamp recordings were used to evaluate neuronal excitability after Ash1L haploinsufficiency in primary sensory neurons.Key ResultsThe haploinsufficiency of ASH1L, a histone methyltransferase, in primary sensory neurons causes both neurite hyperinnervation and increased neuronal excitability, which promote miR-let-7b release from primary afferents in the skin in a neuronal activity-dependent manner. With a 'GUUGUGU' core sequence, miR-let-7b functions as an endogenous ligand of toll-like receptor 7 (TLR7) and stimulates the activation of dermal dendritic cells (DCs) and interleukin (IL)-23/IL-17 axis, ultimately exacerbating the symptoms of psoriasis. Thus, by limiting miR-let-7b release from primary afferents, ASH1L prevents dermal DC activation and ameliorates psoriasis.Conclusion and ImplicationsSomatosensory neuron ASH1L modulates the cutaneous immune system by limiting neuronal activity-dependent release of miR-let-7b, which can directly activate dermal DCs via TLR7 and ultimately lead to aggravated psoriatic lesion.","image"]

关键词Ash1L dendritic cell dorsal root ganglion miRNA neuroimmune interaction psoriasis
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收录类别SCI
语种英语
资助项目STI 2030-Major Projects[2021ZD0203200-01] ; STI 2030 Major Projects[
WOS研究方向Pharmacology & Pharmacy
WOS类目Pharmacology & Pharmacy
WOS记录号WOS:001111279200001
出版者WILEY
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文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/347855
专题生命科学与技术学院
生命科学与技术学院_PI研究组_管吉松组
通讯作者Guan, Ji-Song; Han, Qingjian
作者单位
1.Fudan Univ, State Key Lab Med Neurobiol, Shanghai, Peoples R China
2.Fudan Univ, Huashan Hosp, Inst Brain Sci, MOE Frontiers Ctr Brain Sci,Dept Neurosurg, Shanghai, Peoples R China
3.Fudan Univ, Sch Basic Med Sci, Key Lab Med Mol Virol, MOE,NHC,CAMS,Dept Immunol, Shanghai, Peoples R China
4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
5.Shanghai Univ Tradit Chinese Med, Sch Rehabil Sci, Shanghai, Peoples R China
6.Southern Univ Sci & Technol, Dept Biomed Engn, Shenzhen Key Lab Smart Healthcare Engn, Guangdong Prov Key Lab Adv Biomat, Shenzhen, Peoples R China
7.Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China
8.Fudan Univ, Huashan Hosp, Inst Brain Sci, MOE Frontiers Ctr Brain Sci, Shanghai 200032, Peoples R China
9.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
通讯作者单位生命科学与技术学院
推荐引用方式
GB/T 7714
Du, Wan-Jie,Yang, Huan,Tong, Fang,et al. Ash1L ameliorates psoriasis via limiting neuronal activity-dependent release of miR-let-7b[J]. BRITISH JOURNAL OF PHARMACOLOGY,2023.
APA Du, Wan-Jie.,Yang, Huan.,Tong, Fang.,Liu, Shuai.,Zhang, Chen.,...&Han, Qingjian.(2023).Ash1L ameliorates psoriasis via limiting neuronal activity-dependent release of miR-let-7b.BRITISH JOURNAL OF PHARMACOLOGY.
MLA Du, Wan-Jie,et al."Ash1L ameliorates psoriasis via limiting neuronal activity-dependent release of miR-let-7b".BRITISH JOURNAL OF PHARMACOLOGY (2023).
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