https://orcid.org/0000-0003-1522-3138
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Abstract
Regulatory T (Treg) cells are essential for maintaining self-immune tolerance. Reduced numbers or functions of Treg cells have been involved in the pathogenesis of various autoimmune diseases and allograft rejection. Therefore, the approaches that increase the pool or suppressive function of Treg cells in vivo could be a general strategy to treat different autoimmune diseases and allograft rejection. Interleukin-2 (IL-2) is essential for the development, survival, maintenance, and function of Treg cells, constitutively expressing the high-affinity receptor of IL-2 and sensitive response to IL-2 in vivo. And low-dose IL-2 therapy in vivo could restore the imbalance between autoimmune response and self-tolerance toward self-tolerance via promoting Treg cell expansion and inhibiting follicular helper T (Tfh) and IL-17-producing helper T (Th17) cell differentiation. Currently, low-dose IL-2 treatment is receiving extensive attention in autoimmune disease and transplantation treatment. In this review, we summarize the biology of IL-2/IL-2 receptor, the mechanisms of low-dose IL-2 therapy in autoimmune diseases, the application in the progress of different autoimmune diseases, including Systemic Lupus Erythematosus (SLE), Type 1 Diabetes (T1D), Rheumatoid Arthritis (RA), Autoimmune Hepatitis (AIH), Alopecia Areata (AA), Immune Thrombocytopenia (ITP) and Chronic graft-versus-host-disease (GVHD). We also discuss the future directions to optimize low-dose IL-2 treatments.
GRAPHICAL ABSTRACT
PLAIN LANGUAGE SUMMARY
Low-dose interleukin-2 (IL-2) is a potential treatment for autoimmune diseases. IL-2 is a protein that helps regulate the immune system, and low doses of it can activate regulatory T cells (Tregs), which help control the immune response. This can be beneficial in autoimmune diseases where the immune system attacks healthy tissues. We discuss several clinical trials that have investigated the effectiveness of low-dose IL-2 in treating autoimmune diseases. These trials have shown promising results, with some patients experiencing improvements in symptoms and disease progression. However, more research is needed to determine the safety and effectiveness of low-dose IL-2 as a treatment for autoimmune diseases. IL-2 can also activate other immune cells, which may cause unwanted side effects. Therefore, careful monitoring and dosing are necessary when using this treatment. We should also take note of some of the challenges associated with using low-dose IL-2 as a treatment for autoimmune diseases. For example, it can be difficult to determine the optimal dose and dosing schedule for each patient. In addition, there may be individual differences in how patients respond to low-dose IL-2 treatment. Overall, we believe that low-dose IL-2 shows promise as a treatment for autoimmune diseases, but more research is needed to fully understand its potential benefits and risks.
Author contributions
ES, RZ, YZ and XC drafted the manuscript, and drew the table. ES conceived the topic of the manuscript and revised the content of the manuscript. ZZ and XL helped to search the references and revised the manuscript. All authors approved the publication of the manuscript.
Declaration of Interest
The authors declare no financial or commercial conflict of interest.