Treg Cells in Rheumatoid Arthritis: An Update

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease arising from a breakdown in immunological self-tolerance, which leads to aberrant immune responses to autoantigens. Regulatory CD4(+) T-cells (Tregs) underpin one of the key mechanisms of self-tolerance and are a major focus of study in RA and other autoimmune diseases. In order to design new and improved therapies to reinstate self-tolerance, and perhaps cure disease, we need to understand the complex mechanism of action of Tregs. This review addresses recent findings in the field of Tregs in RA, with particular focus on identification of potential defects in Treg-mediated self-tolerance mechanisms present in RA patients, as well as how Tregs interact with other cells in the inflamed joints. As antigen-specific Tregs are a potential route for the reinstatement of immune tolerance, we also discuss new strategies currently being investigated which expand or induce de novo generation of Tregs.

Changes of Naturally Occurring CD4⁺CD25⁺ FOXP3⁺ Regulatory T Cells in Patients With Acute Coronary Syndrome and the Beneficial Effects of Atorvastatin Treatment

“…[28][29][30] Here, we report a reduced number of nTregs in patients with ACS. We further show that atorvastatin significantly increases the number of nTregs and restores their inhibitory properties, as compared to the vehicle control group.…”

Galectin-3 in autoimmunity and autoimmune diseases

“…60 Indeed, in RA synovitis, the inflammatory process is orchestrated by activated monocytes (secreting IL-1b, IL-6, IL-7 and tumor necrosis factor-alpha (TNF)-a), fibroblast-like synoviocytes (synthesizing metalloproteases, chemokines and cytokines, mainly IL-15), and dysregulated osteoclasts (due to high levels of TNF-a and IL-17). 61 Gal-3 seems to play a pro-inflammatory role in RA 62 and high serum levels of gal-3 have been found in mice during collagen-induced arthritis. 63 In humans, gal-3 mRNA and protein are overexpressed in the synovial membrane close to joint destruction and are highly correlated with C-reactive protein (CRP) serum levels and IL-6, granulocyte-macrophage colony stimulating factor (GM-CSF), chemokine (C-X-C) motif ligand 8 (CXCL8), metalloproteinase-3 (MMP-3), TNF-a, chemokine (C-C motif) ligand 2 (CCL2), CCL3 and CCL5 secretion by synovial fibroblasts.…”

The therapeutic potential of regulatory T cells for the treatment of autoimmune disease

“…Initial studies on the potential of Treg therapies have been conducted in a series of animal models including GvHD, transplantation, MS, RA, T1D, and IBD with good success [5,24,82]. Based on these preclinical studies, we, and others, set out to manufacture Tregs as clinical therapeutics.…”