Targeting Tregs in Juvenile Idiopathic Arthritis and Juvenile Dermatomyositis—Insights From Other Diseases

Abstract

Regulatory T cells (Tregs) are believed to be dysfunctional in autoimmunity. Juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis (JDM) result from a loss of normal immune regulation in specific tissues such as joints or muscle and skin, respectively. Here, we discuss recent findings in regard to Treg biology in oligo-/polyarticular JIA and JDM, as well as what we can learn about Treg-related disease mechanism, treatment and biomarkers in JIA/JDM from studies of other diseases. We explore the potential use of Treg immunoregulatory markers and gene signatures as biomarkers for disease course and/or treatment success. Further, we discuss how Tregs are affected by several treatment strategies already employed in the therapy of JIA and JDM and by alternative immunotherapies such as anti-cytokine or co-receptor targeting. Finally, we review recent successes in using Tregs as a treatment target with low-dose IL-2 or cellular immunotherapy. Thus, this mini review will highlight our current understanding and identify open questions in regard to Treg biology, and how recent findings may advance biomarkers and new therapies for JIA and JDM.

Modification of Intestinal Microbiota Dysbiosis by Low-Dose Interleukin-2 in Dermatomyositis: A Post Hoc Analysis From a Clinical Trial Study

“…Immunological imbalance is considered a vital role in developing IIMs. Tregs are essential to maintaining the balance by suppressing the activation and expansion of auto-reactive T cells and other pathogenic immune cells ( Hoeppli and Pesenacker, 2019 ). We and others have demonstrated the effectiveness of low-dose IL-2 therapy in IIMs, and associated with the expansion of Tregs and inhibition of Teff cells ( Miao et al., 2021 ).…”

Expansion of a novel population of NK cells with low ribosome expression in juvenile dermatomyositis

“…JDM patients have increased T cell skewing towards Th2 and Th17 responses, which correlates with disease activity ( 9 ). Dysregulation of T regulatory cells with restricted diversity has also been implicated in JDM ( 10 ). Innate immune plasmacytoid dendritic cells are present in JDM affected muscle ( 11 ) and may serve as a source of type I interferon (IFN) ( 12 ).…”

The Role of Immune Cells in the Pathogenesis of Idiopathic Inflammatory Myopathies

“…Although existence of Tregs in IIM muscle has been detected [ 30 , 73 ], more attention has been paid to their circulating compartment, and a decreased percentage of Tregs in the peripheral blood of IIM patients has been reported. Among studies to date, the suppressor function of Tregs was normal or impaired [ 74 - 76 ].…”