Forkhead box P3 (FOXP3)

Forkhead box P3 (FOXP3) is a transcription factor that serves as the master regulator for the development and inhibitory function of regulatory T cells (Tregs) [UniProt, Hori et al., 2003]. It belongs to the forkhead/winged-helix family and is primarily expressed in a subset of CD4+ T cells, where it controls the expression of genes essential for immune suppression, such as IL-10 and CTLA-4 [NCBI Gene, Togashi et al., 2019]. FOXP3 is critical for maintaining peripheral tolerance; its deficiency or mutation leads to the development of IPEX syndrome, a severe multi-organ autoimmune disease [StatPearls]. In oncology, FOXP3+ Tregs are often recruited to the tumor microenvironment, where they facilitate immune evasion by inhibiting the activity of cytotoxic T cells and natural killer cells [Togashi et al., 2019]. Consequently, FOXP3 and the cells expressing it are major targets for therapeutic intervention, with strategies focusing on depleting Tregs in cancer or expanding/stabilizing them in autoimmune and inflammatory conditions [Hori et al., 2003; Togashi et al., 2019; Klatzmann & Abbas, 2015].

Modulation of regulatory T cell (Treg) development and suppressive function through transcriptional regulation of immune-related genes, or direct depletion/expansion of FOXP3-expressing cell populations [Hori et al., 2003; Togashi et al., 2019; Klatzmann & Abbas, 2015].