New therapeutic strategies based on IL-2 to modulate Treg cells for autoimmune diseases

Interleukin-2 (IL-2) is a multifunctional cytokine in immune regulation. It is essential for the differentiation, expansion and stability of CD25(+)Foxp3(+) regulatory T (Treg) cells, which is an important factor in immune suppression and self-tolerance. Meanwhile, IL-2 also stimulate effector T (Teff) cells to promote immune responses. The opposite and diverse function of IL-2 impedes its application to boost Treg cell populations in autoimmune disease treatment. Thus, it became focus of the research to modulate IL-2 activities to enhance Treg cell functions selectively. Based on the characteristic properties of Treg cells such as constitutively expression of high affinity IL-2 receptors (IL-2Rs), multiple approaches, including IL-2/mAb complexes, IL-2 muteins and low-dose of IL-2 have emerged in recent years to selectively target Treg cells and treat autoimmunity. These therapeutic approaches have achieved favorable results in both clinical trials and experimental animal models, and provided engineering blueprints to develop novel strategies of IL-2 treatments for autoimmune diseases.