| 内容提要: |
Interleukin 2 (IL-2) is a multifunctional cytokine that keeps the homeostasis of T cell in immune system. The mechanism is that at low-dosage, IL-2 can promote the development and maintenance of regulatory T cells (Treg) which is critical to treat autoimmune diseases, while enhance the functions of effector T cells (Teff) at high-dosage. Treg is sensitive to low level of IL-2 because Treg expresses high-affinity IL-2 receptors (IL-2Rαβγ) constitutively (Fig.1). PTEN, programmed death 1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) expressed in Treg can also maintain Treg stability by inhibiting PI3K-AKT-mTOR axis signal pathway. Currently, a lot of clinical trials demonstrate that low-dosage IL-2 selectively expands Treg without much impact on Teff. Therefore, administration of low-dosage IL-2 is considered a new therapeutic strategy for autoimmune diseases and inflammatory conditions, including Systemic lupus erythematosus (SLE) and Type 1 Diabetes (T1D). In addition, antibodies against IL-2 and IL-2 muteins have also been demonstrated to selectively expand Treg. Therefore, IL-2 , IL-2-antibody and IL-2 muteins are three strategies of IL-2 therapy. |