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Review
. 2021 Apr 1:12:648408.
doi: 10.3389/fimmu.2021.648408. eCollection 2021.

Low-Dose IL-2 Therapy in Autoimmune and Rheumatic Diseases

Hanna Graßhoff  1 , Sara Comdühr  1 , Luisa R Monne  1 , Antje Müller  1 , Peter Lamprecht  1 , Gabriela Riemekasten  1 , Jens Y Humrich  1
Affiliations
Review

Low-Dose IL-2 Therapy in Autoimmune and Rheumatic Diseases

Hanna Graßhoff et al. Front Immunol. .

Abstract

Regulatory T cells (Treg) are crucial for the maintenance of peripheral tolerance and for the control of ongoing inflammation and autoimmunity. The cytokine interleukin-2 (IL-2) is essentially required for the growth and survival of Treg in the peripheral lymphatic tissues and thus plays a vital role in the biology of Treg. Most autoimmune and rheumatic diseases exhibit disturbances in Treg biology either at a numerical or functional level resulting in an imbalance between protective and pathogenic immune cells. In addition, in some autoimmune diseases, a relative deficiency of IL-2 develops during disease pathogenesis leading to a disturbance of Treg homeostasis, which further amplifies the vicious cycle of tolerance breach and chronic inflammation. Low-dose IL-2 therapy aims either to compensate for this IL-2 deficiency to restore a physiological state or to strengthen the Treg population in order to be more effective in counter-regulating inflammation while avoiding global immunosuppression. Here we highlight key findings and summarize recent advances in the clinical translation of low-dose IL-2 therapy for the treatment of autoimmune and rheumatic diseases.

Keywords: autoimmunity; immune regulation; immune tolerance; immunotherapy; inflammation; interleukin-2; regulatory T cell.

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Conflict of interest statement

GR and JH are members of the steering committee for a currently ongoing multi-center phase 2 clinical trial on low-dose IL-2 therapy in SLE (LUPIL-2) sponsored by ILTOO Pharma. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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