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N6-methyladenosine modification-tuned lipid metabolism controls skin immune homeostasis via regulating neutrophil chemotaxis.
Cui, Lian; Wu, You; Chen, Zeyu; Li, Bingjie; Cai, Jiangluyi; Chang, Zhanhe; Xiao, Weide; Wang, Yuanyuan; Yang, Nan; Wang, Yu; Yu, Zengyang; Yao, Lingling; Ma, Rui; Wang, Xin; Chen, Youdong; Chen, Qianyu; Mei, Hao; Lan, Zhiyi; Yu, Yingyuan; Chen, Rongfen; Wu, Xingbiao; Yu, Qian; Lu, Jiajing; Yu, Ning; Zhang, Xilin; Liu, Jun; Zhang, Lingjuan; Lai, Yuping; Gao, Shaorong; Gao, Yawei; Guo, Chunyuan; Shi, Yuling.
Afiliação
  • Cui L; Department of Dermatology, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.
  • Wu Y; Institute of Psoriasis, School of Medicine, Tongji University, Shanghai, China.
  • Chen Z; Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
  • Li B; Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China.
  • Cai J; Department of Dermatology, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.
  • Chang Z; Institute of Psoriasis, School of Medicine, Tongji University, Shanghai, China.
  • Xiao W; Department of Dermatology, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.
  • Wang Y; Institute of Psoriasis, School of Medicine, Tongji University, Shanghai, China.
  • Yang N; CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • Wang Y; Department of Dermatology, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.
  • Yu Z; Institute of Psoriasis, School of Medicine, Tongji University, Shanghai, China.
  • Yao L; Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
  • Ma R; Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China.
  • Wang X; State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China.
  • Chen Y; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
  • Chen Q; Department of Dermatology, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.
  • Mei H; Institute of Psoriasis, School of Medicine, Tongji University, Shanghai, China.
  • Lan Z; Department of Dermatology, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.
  • Yu Y; Institute of Psoriasis, School of Medicine, Tongji University, Shanghai, China.
  • Chen R; Department of Dermatology, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.
  • Wu X; Institute of Psoriasis, School of Medicine, Tongji University, Shanghai, China.
  • Yu Q; Institute of Psoriasis, School of Medicine, Tongji University, Shanghai, China.
  • Lu J; Department of Dermatology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
  • Yu N; Department of Dermatology, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.
  • Zhang X; Institute of Psoriasis, School of Medicine, Tongji University, Shanghai, China.
  • Liu J; Department of Dermatology, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.
  • Zhang L; Institute of Psoriasis, School of Medicine, Tongji University, Shanghai, China.
  • Lai Y; Department of Dermatology, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.
  • Gao S; Institute of Psoriasis, School of Medicine, Tongji University, Shanghai, China.
  • Gao Y; Department of Dermatology, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.
  • Guo C; Institute of Psoriasis, School of Medicine, Tongji University, Shanghai, China.
  • Shi Y; Department of Dermatology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Sci Adv ; 10(40): eadp5332, 2024 Oct 04.
Article em En | MEDLINE | ID: mdl-39356764
ABSTRACT
Disrupted N6-methyladenosine (m6A) modification modulates various inflammatory disorders. However, the role of m6A in regulating cutaneous inflammation remains elusive. Here, we reveal that the m6A and its methyltransferase METTL3 are down-regulated in keratinocytes in inflammatory skin diseases. Inducible deletion of Mettl3 in murine keratinocytes results in spontaneous skin inflammation and increases susceptibility to cutaneous inflammation with activation of neutrophil recruitment. Therapeutically, restoration of m6A alleviates the disease phenotypes in mice and suppresses inflammation in human biopsy specimens. We support a model in which m6A modification stabilizes the mRNA of the lipid-metabolizing enzyme ELOVL6 via the m6A reader IGF2BP3, leading to a rewiring of fatty acid metabolism with a reduction in palmitic acid accumulation and, consequently, suppressing neutrophil chemotaxis in cutaneous inflammation. Our findings highlight a previously unrecognized epithelial-intrinsic m6A modification-lipid metabolism pathway that is essential for maintaining epidermal and immune homeostasis and lay the basis for potential therapeutic targeting of m6A modulators to attenuate inflammatory skin diseases.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pele / Queratinócitos / Adenosina / Metabolismo dos Lipídeos / Homeostase / Metiltransferases / Neutrófilos Limite: Animals / Humans Idioma: En Revista: Sci Adv Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pele / Queratinócitos / Adenosina / Metabolismo dos Lipídeos / Homeostase / Metiltransferases / Neutrófilos Limite: Animals / Humans Idioma: En Revista: Sci Adv Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China