The Impact of Akkermansia muciniphila and Its Outer Membrane Vesicles on MicroRNA Expression in Human Dendritic Cells
Researchers at the Pasteur Institute of Iran, led by Seyed Davar Siadat, investigated the effects of Akkermansia muciniphila and its outer membrane vesicles (OMVs) on the expression of key microRNAs involved in inflammatory and anti-inflammatory pathways in human dendritic cells (DCs).
Probiotics, such as A. muciniphila, are known for their role in immunomodulation by influencing DC maturation and inducing tolerogenic DCs. The study aimed to assess whether A. muciniphila and its OMVs could modulate the expression of microRNA-155, microRNA-146a, microRNA-34a, and let-7i, which are pivotal in regulating inflammation.
Peripheral blood mononuclear cells (PBMCs) were isolated from healthy volunteers and differentiated into DCs. These DCs were then treated with various substances, including A. muciniphila, OMVs, lipopolysaccharide (LPS), and dexamethasone, among others. Flow cytometry was used to analyze surface marker expression, while qRT-PCR and ELISA were employed to measure microRNA expression and cytokine levels, respectively.
Results showed that A. muciniphila treatment, particularly at higher multiplicities of infection (MOIs), significantly reduced the levels of pro-inflammatory cytokine IL-12 compared to the LPS-stimulated group. Conversely, IL-10, an anti-inflammatory cytokine, was increased upon treatment with A. muciniphila and its OMVs. Moreover, A. muciniphila and OMVs were able to reverse the upregulation of microRNA-155, microRNA-34a, and microRNA-146a induced by LPS treatment. Additionally, let-7i expression increased in treatment groups compared to the LPS-stimulated group.
Furthermore, A. muciniphila treatment influenced the expression of surface markers associated with DC maturation and tolerogenicity, suggesting the induction of tolerogenic DCs and promotion of anti-inflammatory responses.
This study sheds light on the immunomodulatory properties of A. muciniphila and its OMVs, highlighting their potential therapeutic applications in inflammatory disorders.