Short-chain fatty acids stimulate dendrite elongation in dendritic cells by inhibiting histone deacetylase.
Rho family GTPase
dendrite elongation
dendritic cell
histone deacetylase
short-chain fatty acid
Journal
The FEBS journal
ISSN: 1742-4658
Titre abrégé: FEBS J
Pays: England
ID NLM: 101229646
Informations de publication
Date de publication:
30 Aug 2023
30 Aug 2023
Historique:
revised:
08
07
2023
received:
27
02
2023
accepted:
29
08
2023
pubmed:
30
8
2023
medline:
30
8
2023
entrez:
30
8
2023
Statut:
aheadofprint
Résumé
Dendritic cells activate immune responses by presenting pathogen-derived molecules. The dendrites of dendritic cells contribute to the incorporation of foreign antigens or presenting antigens to T cells. Short-chain fatty acids (SCFAs), such as acetic, propionic, butyric and valeric acids, have many effects on immune responses by activating specific receptors or inhibiting a histone deacetylase (HDAC), although their effect on dendrite formation in dendritic cells is unknown. In the present study, we aimed to investigate the effect of SCFAs on dendrite elongation using a dendritic cell line (DC2.4 cells) and mouse bone marrow-derived dendritic cells. We found that SCFAs induced dendrite elongation. The elongation was reduced by inhibitors of Src family kinase (SFK), phosphatidylinositol-3 kinase (PI3K), Rho family GTPases (Cdc42, Rac1) or actin polymerization, indicating that SCFAs promote dendrite elongation by activating actin polymerization via the SFK/PI3K/Rho family GTPase signaling pathway. We showed that agonists for SCFA receptors GPR43 and GPR109a did not promote dendrite elongation. By contrast, HDAC inhibitors, including trichostatin A, promoted dendrite elongation in DC2.4 cells, and the promoting activity of trichostatin A was decreased by inhibiting the SFK/PI3K/Rho family GTPase signaling pathway or actin polymerization. Furthermore, DC2.4 cells treated with valeric acid showed enhanced uptake of soluble proteins, insoluble beads and Staphylococcus aureus. We also found that treatment with valeric acid enhanced major histocompatibility complex class II-mediated antigen presentation in bone marrow-derived dendritic cells. These results suggest that SCFAs promote dendrite elongation by inhibiting HDAC, stimulating the SFK/PI3K/Rho family pathway and activating actin polymerization, resulting in increased antigen uptake and presentation in dendritic cells.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Japan Society for the Promotion of Science
ID : 20K07030
Organisme : Japan Society for the Promotion of Science
ID : 22H02869
Organisme : Japan Society for the Promotion of Science
ID : 22K19435
Organisme : Japan Society for the Promotion of Science
ID : 23K06130
Organisme : Takeda Science Foundation
Informations de copyright
© 2023 Federation of European Biochemical Societies.
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