Internal Peacekeepers And External Mediators: A New Model Of Peripheral Immune Tolerance Involving Regulatory T Cells And Mesenchymal Stem Cells

The document proposes a two-tier model of peripheral immune tolerance involving regulatory T cells (Tregs) and mesenchymal stem/stromal cells (MSCs). Tregs act as an "internal checkpoint" within the immune system to moderate effector cell activity, while MSCs function as an "external checkpoint," activated by inflammation to secrete immunomodulatory molecules, promote tissue repair, and reduce excessive immune activity. This model highlights the essential roles of Tregs and MSCs in preventing autoimmunity and tissue damage, explaining autoimmune pathophysiology and tumor immune evasion, and suggesting the therapeutic potential of MSC-based treatments.