Mesenchymal stromal cells reprogram monocytes and macrophages with processing bodies

Area of Science:

• Immunology
• Cell Biology
• Regenerative Medicine

Background:

• Mesenchymal stromal cells (MSCs) show variable success in modulating inflammation due to poorly understood mechanisms.
• MSCs are rapidly cleared after administration but exert long-term anti-inflammatory effects.

Purpose of the Study:

• To elucidate the mechanism by which human cord tissue-derived MSCs (hCT-MSCs) suppress inflammation.
• To investigate the role of RNA processing bodies (p-bodies) in MSC-mediated immune reprogramming.

Main Methods:

• hCT-MSCs were used to treat monocytes and macrophages in vitro and in vivo.
• p-body deficient hCT-MSCs were generated to assess their functional impact.
• Inflammation was induced via nasal lipopolysaccharide challenge in a mouse model.

Main Results:

• hCT-MSCs reprogrammed monocytes and macrophages, downregulating antigen presentation and costimulation genes, thereby suppressing T-cell activation.
• Low-density lipoprotein receptor-related proteins mediated the engulfment of hCT-MSCs by immune cells.
• p-body deficient hCT-MSCs failed to reprogram immune cells and suppress lipopolysaccharide-induced lung inflammation, with persistent MHC-II expression.

Conclusions:

• hCT-MSCs reprogram monocytes and macrophages through p-bodies, representing a novel mechanism for indirect T-cell suppression.
• This p-body-mediated reprogramming is critical for the long-term anti-inflammatory effects of MSCs.
• Understanding this mechanism could improve the efficacy of MSC-based therapies.