Acid ceramidase regulates innate immune memory.
Cell Rep
; 42(12): 113458, 2023 12 26.
Article
em En
| MEDLINE
| ID: mdl-37995184
ABSTRACT
Innate immune memory, also called "trained immunity," is a functional state of myeloid cells enabling enhanced immune responses. This phenomenon is important for host defense, but also plays a role in various immune-mediated conditions. We show that exogenously administered sphingolipids and inhibition of sphingolipid metabolizing enzymes modulate trained immunity. In particular, we reveal that acid ceramidase, an enzyme that converts ceramide to sphingosine, is a potent regulator of trained immunity. We show that acid ceramidase regulates the transcription of histone-modifying enzymes, resulting in profound changes in histone 3 lysine 27 acetylation and histone 3 lysine 4 trimethylation. We confirm our findings by identifying single-nucleotide polymorphisms in the region of ASAH1, the gene encoding acid ceramidase, that are associated with the trained immunity cytokine response. Our findings reveal an immunomodulatory effect of sphingolipids and identify acid ceramidase as a relevant therapeutic target to modulate trained immunity responses in innate immune-driven disorders.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ceramidase Ácida
/
Imunidade Treinada
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Holanda