IL-2-based approaches to Treg enhancement
Open Access
- 18 November 2022
- journal article
- review article
- Published by Oxford University Press (OUP) in Clinical and Experimental Immunology
- Vol. 211 (2), 149-163
- https://doi.org/10.1093/cei/uxac105
Abstract
Immune homeostasis is heavily dependent on the action of regulatory T cells (Tregs) which act to suppress the activation of many immune cell types including autoreactive conventional T cells. A body of evidence has shown that Tregs are intrinsically defective in many common autoimmune diseases, and gene polymorphisms which increase the susceptibility of autoimmune disease development have implicated the interleukin-2 (IL-2) signalling pathway as a key dysregulated mechanism. IL-2 is essential for Treg function and survival, and Tregs are highly sensitive to low levels of this cytokine in their environment. This review will revisit the rationale behind using low-dose IL-2 as a therapy to treat autoimmune diseases and evaluate the outcomes of trials to date. Furthermore, novel engineered IL-2 therapies with increased Treg specificity have shown promise in pre-clinical studies and human clinical trials for some agents have begun. Future studies will determine whether low-dose IL-2 or engineered IL-2 therapies can change the course of autoimmune and inflammatory diseases in patients.Keywords
Funding Information
- Innovative Medicines Initiative (115797)
- Leona M. and Harry B. Helmsley Charitable Trust (115797)
- Medical Research Council (115797)
- National Institute for Health Research
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