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

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

SUBMITTER: Cui L 

PROVIDER: S-EPMC11446281 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature