Restoring regulation - IL-2 therapy in systemic lupus erythematosus.
The pathogenesis of systemic lupus erythematosus (SLE) involves an acquired deficiency of the cytokine IL-2, an essential growth and survival factor for regulatory T cells (Treg), which play an important role in the control of autoimmunity in SLE. In contrast to currently available therapies that broadly suppress the immune system, low-dose IL-2 therapy in SLE aims to compensate the pre-existing IL-2 deficiency and thus to restore a physiological state, where Treg can regain their ability to efficiently counteract autoimmunity. Areas covered: Here we summarize key findings that led to the development of this novel therapeutic concept and will highlight the key rationales for the clinical translation of low-dose IL-2 therapy in SLE. Expert commentary: The concept of low-dose IL-2 therapy in SLE has evolved from pathophysiological findings and thus can be considered a selective biological treatment strategy in SLE. Preliminary results from phase I/II studies are promising by proving selective Treg expansion and by providing first evidence for the clinical efficacy of low-dose IL-2 therapy in SLE.
a Department of Rheumatology , University Hospital Schleswig-Holstein , Lübeck , Germany.
Jens Y
JY
Humrich
a Department of Rheumatology , University Hospital Schleswig-Holstein , Lübeck , Germany.
Gabriela
G
Riemekasten
D000818:Animals; D015551:Autoimmunity / Q000187:drug effects; D002986:Clinical Trials as Topic; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D007167:Immunotherapy / Q000379:methods*; D007376:Interleukin-2 / Q000276:immunology / Q000627:therapeutic use*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000628:therapy*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007376:Interleukin-2
SLE; immune homeostasis; immunotherapy; interleukin-2; regulatory T cell; systemic lupus erythematosus; tolerance