Targeting IL-2: an unexpected effect in treating immunological diseases

Abstract

Regulatory T cells (Treg) play a crucial role in maintaining immune homeostasis since Treg dysfunction in both animals and humans is associated with multi-organ autoimmune and inflammatory disease. While IL-2 is generally considered to promote T-cell proliferation and enhance effector T-cell function, recent studies have demonstrated that treatments that utilize low-dose IL-2 unexpectedly induce immune tolerance and promote Treg development resulting in the suppression of unwanted immune responses and eventually leading to treatment of some autoimmune disorders. In the present review, we discuss the biology of IL-2 and its signaling to help define the key role played by IL-2 in the development and function of Treg cells. We also summarize proof-of-concept clinical trials which have shown that low-dose IL-2 can control autoimmune diseases safely and effectively by specifically expanding and activating Treg. However, future studies will be needed to validate a better and safer dosing strategy for low-dose IL-2 treatments utilizing well-controlled clinical trials. More studies will also be needed to validate the appropriate dose of IL-2/anti-cytokine or IL-2/anti-IL-2 complex in the experimental animal models before moving to the clinic.

Immunotherapy: Interleukin-2 therapy promising for autoimmune disease

Low doses of the immune signaling molecule interleukin-2 (IL-2) could help suppress unwanted immune responses in patients with autoimmunity. Song Zheng from Penn State Health Milton S. Hershey Medical Center, USA and Sun Yat-sen University, and colleagues reviewed the key role that IL-2 plays in the development and function of regulatory T cells, a type of suppressive immune cell that keeps the rest of the immune system in check. The researchers summarized data from proof-of-concept clinical trials, which showed that, at low doses, IL-2 is well tolerated and induces regulatory T cells to address immune imbalances in patients with lupus, type 1 diabetes and other autoimmune disorders. However, the researchers suggest that IL-2 treatments might need to be combined with other immune-modulating strategies to maximize the therapeutic benefit while minimizing side effects.