DOI: 10.1111/febs.16945 ISSN:

Short‐chain fatty acids stimulate dendrite elongation in dendritic cells by inhibiting histone deacetylase

Takuho Inamoto, Kazuyuki Furuta, Cheng Han, Mio Uneme, Tomonori Kano, Kazuya Ishikawa, Chikara Kaito
  • Cell Biology
  • Molecular Biology
  • Biochemistry

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), but their effect on dendrite formation in dendritic cells is unknown. In this 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 (BMDCs). We found that SCFAs induced dendrite elongation. The elongation was reduced by inhibitors of Src family kinase (SFK), 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. In contrast, HDAC inhibitors, including trichostatin A (TSA), promoted dendrite elongation in DC2.4 cells, and the promoting activity of TSA 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 MHC‐II‐mediated antigen presentation in BMDCs. 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.

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