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Dendritic cells are immune cells that capture and present antigens to T cells, activating an immune response. Researchers from Okayama University have discovered that short-chain fatty acids produced by intestinal bacteria regulate a crucial step in this process, the extension of dendritic “arms.” This breakthrough finding could potentially lead to the development of disease prevention strategies involving beneficial bacteria and new drugs targeting the regulation of dendritic cell function.
Dendritic cells play a key role in the mammalian immune system. These cells are present throughout the human body and are known to capture foreign bodies, i.e., antigens, using extendable “arms” called dendrites. Once captured, dendritic cells present these substances to immune T cells, thereby initiating an immune response. Dendritic cells are responsive to their environment and capable of changing their morphology and other attributes dynamically. For instance, dendritic cells in the intestine’s mucosa (inner layer) capture harmful bacteria by extending their dendrites through the epithelium (outermost layer) and into the intestinal lumen (inner space). However, the exact mechanism through which they do is not clear.
In a study that was published in The FEBS Journal on August 30, 2023, a team of researchers led by Associate Professor Kazuyuki Furuta, Mr. Takuho Inamoto, Dr. Kazuya Ishikawa, and Dr. Chikara Kaito from the Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences at Okayama University, Japan found that short-chain fatty acids (SCFAs) produced by intestinal bacteria are responsible for initiating the extension of dendrites into the intestinal lumen by dendritic cells.
SCFAs are a group of fatty acids with six or fewer carbon atoms, found in high concentrations in the intestine. The research team found that SCFAs such as acetic, propionic, butyric and valeric acids induce dendrite elongation by inhibiting an enzyme called histone deacetylase. Inhibition of histone deacetylase leads to the reorganization of the actin cytoskeleton of dendritic cells, inducing morphological changes. To arrive at these findings, the team examined the effects of SCFAs on a dendritic cell line (DC2.4 cells) and mouse bone marrow-derived dendritic cells (BMDCs) in a laboratory setting.
“Ours is the first study to demonstrate that SCFAs induce dendrite elongation by inhibiting histone deacetylase. Moreover, dendritic cells activated by SCFAs exhibited more stronger immune responses, due to increased pathogen uptake,” explains Dr. Furuta.
Upon conducting further analyses, the team found that treating dendritic cells with valeric acid led to an increase in the uptake of soluble proteins, insoluble beads, and Staphylococcus aureus bacteria. In contrast, the treatment of BMDCs with valeric acid enhanced their antigen presentation ability. It was also observed that SCAFs activated dendrite elongation by stimulating a signaling pathway involved in reorganization of the actin cytoskeleton — forces responsible for cell movement and cell morphology. So, what are the implications of these findings? “Our findings may be leveraged to identify beneficial intestinal bacteria producing SCFAs to activate immune responses and aid in the prevention of diseases. In addition, the dendritic elongation mechanism we discovered can be used as a target to develop drugs regulate immune responses artificially,” remarks Dr. Furuta.
By revealing the exact mechanism through which SCFAs trigger dendritic elongation, this study has paved the way for new drugs that directly target dendritic cells. We cannot wait to see these new treatments unfold!