Abstract The levels of the co-transcriptional regulator IRF2BP2 (Interferon Regulatory Factor-2 Binding Protein-2) decrease with T cell activation and, when ectopically expressed, it reduces T cell proliferation. To further characterize the function of IRF2BP2 in T cell responses in vivo, we generated a conditional transgenic knock-in mouse that overexpresses IRF2BP2 in T lymphocytes. Overexpression of IRF2BP2 leads to a reduction in the T cell compartment of naive animals, upregulation of Foxp3 and Ifng ; an increase in the frequency of regulatory T cells (Tregs), a preferential Th1 differentiation with increase of IFN-γ production and a reduction of T cell proliferation, suggesting a disruption in T cell homeostasis. Interestingly, knock-in mice displayed reduced clinical and inflammatory signs of Experimental Autoimmune Encephalomyelitis (EAE) when compared to the control mice, with an augmented frequency of Treg cells. Altogether, our findings indicate that IRF2BP2 might help to control exacerbated T cell responses and point to a role for IRF2BP2 in preventing T cell autoimmunity.

The transcriptional cofactor IRF2BP2 plays a key role in T cell homeostasis and Treg cell expansion