Regulatory T-cell upregulation (Treg upregulation)

Regulatory T-cell (Treg) upregulation is a biological process and therapeutic strategy focused on increasing the population or suppressive activity of Tregs to restore immune homeostasis [1, 5]. Tregs, characterized by the expression of CD25 and the transcription factor FOXP3, play a critical role in preventing autoimmune diseases and chronic inflammation by suppressing effector T-cell responses [2, 5]. In clinical settings, upregulating Tregs is a primary objective for treating conditions such as graft-versus-host disease (GVHD), Type 1 diabetes, and systemic lupus erythematosus [7, 9]. This is often achieved through the administration of low-dose Interleukin-2 (IL-2), which selectively targets the high-affinity IL-2 receptor on Tregs, or through agents like sirolimus that promote Treg survival [1, 8]. However, in the context of oncology, Treg upregulation within the tumor microenvironment is a major hurdle, as it facilitates immune evasion and promotes tumor progression [2, 3, 6]. Consequently, while Treg upregulation is beneficial for autoimmunity, it must be carefully managed to avoid systemic immunosuppression or the unintended promotion of malignancy [4, 9].

Other names

Treg expansionRegulatory T-cell inductionTreg activationTreg recruitment

Therapeutic upregulation of regulatory T cells (Tregs) typically involves the selective activation of the IL-2 signaling pathway using low-dose cytokines or the use of immunosuppressants that favor Treg differentiation over effector T cells, thereby suppressing pathological immune responses [1, 7, 8].