Ash1L ameliorates psoriasis via limiting neuronal activity-dependent release of miR-let-7b

Du, Wan-Jie1,2; Yang, Huan1,2; Tong, Fang1,2; Liu, Shuai1,2; Zhang, Chen1,2; Chen, Yeying3; Yan, Yuze4; Xiang, Yan-Wei5; Hua, Ling-Yang1,2; Gong, Ye1,2; Xu, Zhi-Xiang1,2; Liu, Xiaoyan6; Jiang, Xingyu6; Lu, Mingfang3; Guan, Ji-Song4,9; Han, Qingjian1,2,7,8

2023-11-01

10.1111/bph.16254

BRITISH JOURNAL OF PHARMACOLOGY   影响因子和分区

0007-1188

1476-5381

["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"]

Ash1L dendritic cell dorsal root ganglion miRNA neuroimmune interaction psoriasis

SCI

英语

其他

STI 2030-Major Projects[2021ZD0203200-01] ; STI 2030 Major Projects["81971034","32271047"] ; National Natural Science Foundation of China[22ZR1413800] ; Natural Science Foundation of Shanghai[2018SHZDZX01] ; Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning, Shanghai Municipal Science and Technology Major Project[ZYYCXTD-C-202008] ; Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine[2020-RGZN-02038] ; Shanghai Artificial Intelligence Innovation and Development Project-Intelligent Dermatology Clinic Based on Modern TCM Diagnostic Technology[LG-QS-202203-12]

Pharmacology & Pharmacy

Pharmacology & Pharmacy

WOS:001111279200001

WILEY

PHARMACOLOGY & TOXICOLOGY

2-s2.0-85178422096

Web of Science

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

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,2023,181(7):1107-1127.

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,181(7),1107-1127.

Du, Wan-Jie,et al."Ash1L ameliorates psoriasis via limiting neuronal activity-dependent release of miR-let-7b".BRITISH JOURNAL OF PHARMACOLOGY 181.7(2023):1107-1127.