Figure 1.

Treg cell mechanisms of action in autoimmunity and therapeutic application. (A) Treg cells are thought to work via four main routes. Route 1: Treg cells expand and secrete large amounts of IL-10, enhancing tolerogenic APC activity. Tolerogenic APCs in turn interact with CD4⁺ T cells, inhibiting their release of self-inflammatory cytokines. In addition, tolerogenic APCs stimulate the development of a regulatory phenotype in naïve T cells and induce the production of Treg cells, ultimately suppressing autoimmune reactions. Route 2: The release of IL-2 in the microenvironment is detected by CD25⁺ Treg cells, which interact with and induce PD-L1 expression in APCs. PD-L1⁺ APCs then induce apoptosis in activated PD-1⁺ Teff cells via PD-1/PD-L1 signaling, inhibiting immune responses, such as those targeting self-antigens. Route 3: The interaction of Treg cells with autoreactive B cells induces B cell apoptosis via perforin/granzyme-mediated cytotoxicity, preventing autoantibody production. Route 4: Treg cells convert extracellular ATP into adenosine (ADO), a potent immunosuppressant, using ectoenzymes CD39 and CD73. ADO binds to its receptor in Teff cells, inhibiting them. (B) Any disruption in routes 1, 2, 3, and 4 can lead to autoimmunity. In Treg cell-based therapy, Treg cells are collected from peripheral blood, activated, and expanded ex vivo. Finally, Treg cells are injected to suppress immune responses via routes 1, 2, 3, and 4.