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IL-17D-induced inhibition of DDX5 expression in keratinocytes amplifies IL-36R-mediated skin inflammation.
Ni, Xinhui; Xu, Yi; Wang, Wang; Kong, Baida; Ouyang, Jian; Chen, Jiwei; Yan, Man; Wu, Yawei; Chen, Qi; Wang, Xinxin; Li, Hongquan; Gao, Xiaoguang; Guo, Hongquan; Cui, Lian; Chen, Zeyu; Shi, Yuling; Zhu, Ronghui; Li, Wei; Shi, Tieliu; Wang, Lin-Fa; Huang, Jinling; Dong, Chen; Lai, Yuping.
Afiliação
  • Ni X; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.
  • Xu Y; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.
  • Wang W; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.
  • Kong B; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.
  • Ouyang J; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.
  • Chen J; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.
  • Yan M; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.
  • Wu Y; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.
  • Chen Q; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.
  • Wang X; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.
  • Li H; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.
  • Gao X; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.
  • Guo H; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.
  • Cui L; Department of Dermatology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
  • Chen Z; Department of Dermatology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
  • Shi Y; Department of Dermatology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
  • Zhu R; Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.
  • Li W; Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
  • Shi T; Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
  • Wang LF; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.
  • Huang J; Emerging Infectious Diseases Program, Duke-NUS Graduate Medical School, Singapore, Singapore.
  • Dong C; Singhealth Duke-NUS Global Health Institute, Singapore, Singapore.
  • Lai Y; Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China.
Nat Immunol ; 23(11): 1577-1587, 2022 Nov.
Article em En | MEDLINE | ID: mdl-36271146
Aberrant RNA splicing in keratinocytes drives inflammatory skin disorders. In the present study, we found that the RNA helicase DDX5 was downregulated in keratinocytes from the inflammatory skin lesions in patients with atopic dermatitis and psoriasis, and that mice with keratinocyte-specific deletion of Ddx5 (Ddx5∆KC) were more susceptible to cutaneous inflammation. Inhibition of DDX5 expression in keratinocytes was induced by the cytokine interleukin (IL)-17D through activation of the CD93-p38 MAPK-AKT-SMAD2/3 signaling pathway and led to pre-messenger RNA splicing events that favored the production of membrane-bound, intact IL-36 receptor (IL-36R) at the expense of soluble IL-36R (sIL-36R) and to the selective amplification of IL-36R-mediated inflammatory responses and cutaneous inflammation. Restoration of sIL-36R in Ddx5∆KC mice with experimental atopic dermatitis or psoriasis suppressed skin inflammation and alleviated the disease phenotypes. These findings indicate that IL-17D modulation of DDX5 expression controls inflammation in keratinocytes during inflammatory skin diseases.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Psoríase / Dermatite Atópica / Interleucina-27 Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Psoríase / Dermatite Atópica / Interleucina-27 Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article