Trained murine mesenchymal stem cells have anti-inflammatory effect on macrophages, but defective regulation on T-cell proliferation

What is it about?

The memory of the immune system is defined as a protective mechanism to microbial infections, as the secondary response is usually faster and stronger than the response to initial exposure. The "memory" was thought to only exist in lymphocytes, which can recognize microbial ligands and eliminate infiltrated pathogens as well as infected cells. This concept was recently challenged by the observation that intermittent, repeated microbial ligand stimulations induced enhanced or tolerated responses in other immune cells including macrophages. However, the potential regulation of "immune memory" in non-classical immune cells, such as mesenchymal stem cells (MSCs), has not been reported. MSCs are a unique cell population that can modulate both lymphocyte and macrophage-mediated immune responses. The response of MSCs to environmental cues, such as bacterial infections, debris from damaged tissues, and inflammatory mediators, are crucial for the resolution of inflammation, as well as successful tissue healing and repair. In the current study, we observed that the bacterial ligand-trained MSCs, three days after a washout period following primary stimulation, showed a stronger protective response to suppress the inflammatory reaction in macrophages. In contrast, the trained MSCs failed to regulate T lymphocyte proliferation under secondary inflammatory stimulation. Our results demonstrate differential immunomodulatory effects of trained MSCs on macrophages and T lymphocytes. These immunomodulatory consequences are critical, as they will have a major impact on current MSC-based cell therapies.

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