2. Academic Validation
  3. N6-methyladenosine modification-tuned lipid metabolism controls skin immune homeostasis via regulating neutrophil chemotaxis

N6-methyladenosine modification-tuned lipid metabolism controls skin immune homeostasis via regulating neutrophil chemotaxis

  • Sci Adv. 2024 Oct 4;10(40):eadp5332. doi: 10.1126/sciadv.adp5332.
Lian Cui 1 2,  You Wu 3 4,  Zeyu Chen 1 2,  Bingjie Li 1 2 5,  Jiangluyi Cai 1 2,  Zhanhe Chang 3 4,  Weide Xiao 6 7,  Yuanyuan Wang 1 2,  Nan Yang 1 2,  Yu Wang 1 2,  Zengyang Yu 2 8,  Lingling Yao 1 2,  Rui Ma 1 2,  Xin Wang 1 2,  Youdong Chen 1 2 8,  Qianyu Chen 1 2,  Hao Mei 2 8,  Zhiyi Lan 2 8,  Yingyuan Yu 1 2,  Rongfen Chen 1 2,  Xingbiao Wu 1,  Qian Yu 2 8,  Jiajing Lu 1 2,  Ning Yu 1 2,  Xilin Zhang 1 2,  Jun Liu 6 7,  Lingjuan Zhang 9,  Yuping Lai 10,  Shaorong Gao 4 11,  Yawei Gao 3 4,  Chunyuan Guo 1 2,  Yuling Shi 1 2
Affiliations

Affiliations

  • 1 Department of Dermatology, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.
  • 2 Institute of Psoriasis, School of Medicine, Tongji University, Shanghai, China.
  • 3 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.
  • 4 Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China.
  • 5 CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • 6 State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China.
  • 7 Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
  • 8 Department of Dermatology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
  • 9 State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China.
  • 10 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.
  • 11 Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Tongji University, Shanghai, China.
PMID: 39356764 DOI: 10.1126/sciadv.adp5332
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.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z