Suppressive oligodeoxynucleotides promote the generation of regulatory T cells by inhibiting STAT1 phosphorylation

Suppressive oligodeoxynucleotides (Sup ODN) express repetitive TTAGGG motifs that have proven useful in the treatment/prevention of numerous inflammatory and autoimmune diseases. The mechanism underlying the immunosuppressive activity of Sup ODN is incompletely understood. Regulatory T cells (Treg) play a key role in controlling a variety of pathologic autoimmune responses. Treg are generated from activated CD4+ T cells in a process that involves the phosphorylation of STAT family members. Current studies demonstrate that Sup ODN promote the differentiation of CD4+CD25− T cells into functionally active iTreg in vitro. When administered in vivo, Sup ODN promote the generation of iTreg in response to peptide challenge. Central to this effect is the ability of Sup ODN to block the phosphorylation of STAT1. These findings clarify the mechanism underlying the therapeutic activity of Sup ODN and support their use in Treg-based immunotherapy.