Abstract
Regulatory T cells (Tregs) are central in integration and maintenance of immune homeostasis. Since breakdown of self-tolerance is a major culprit in the pathogenesis of systemic lupus erythematosus (SLE), restoration of the immune tolerance through the manipulation of Tregs can be exploited to treat patients with SLE. New information has revealed that Tregs besides their role in suppressing the immune response are important in tissue protection and regeneration. Expansion of Tregs with low-dose IL-2 represents an approach to control the autoimmune response. Moreover, control of Treg metabolism can be exploited to restore or improve their function. Here, we summarize the function and diversity of Tregs and recent strategies to improve their function in patients with SLE.
Highlights
Breakdown of self-tolerance is critical in the development of systemic lupus erythematosus (SLE) [1]
Because IL-2 receptor-dependent activation of transcription factor STAT5 is essential for the suppressive function of Tregs, decreased expression of CD25 may affect the function of Tregs in SLE patients
Further analysis using mass cytometry of low-dose IL-2 treatment in chronic graft-versus-host disease (cGVHD) patients revealed that CD4+CD25+Foxp3+Helios+ Tregs and CD56brightCD16- NK cells were selectively expanded [68]
Summary
Breakdown of self-tolerance is critical in the development of systemic lupus erythematosus (SLE) [1]. Because IL-2 receptor-dependent activation of transcription factor STAT5 is essential for the suppressive function of Tregs, decreased expression of CD25 may affect the function of Tregs in SLE patients. They conducted a combined phase I/IIa clinical trial to address the safety, tolerability, efficacy, and immune response of low-dose IL-2 therapy in patients with active and refractory SLE (PRO-IMMUN, EudraCT-number: 2013001599-40, Germany) [66].
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