Evidence for the role of an altered redox state in hyporesponsiveness of synovial T cells in rheumatoid arthritis.

Abstract

In rheumatoid arthritis (RA), T cells isolated from the synovial fluid (SF) show impaired responses to mitogenic stimulation compared with T cells from the peripheral blood (PB). Here it is reported that hyporesponsiveness of SF T cells correlated with a significant decrease in the levels of the intracellular redox-regulating agent glutathione (GSH). GSH was decreased in both CD4+ (p = 0.0022) and CD8+ (p = 0.0010) SF T cell subsets compared with PB CD4+ and CD8+ T cells in RA patients. Levels of thioredoxin (TRX), another key redox mediator, previously found to be secreted under conditions of oxidative stress, were found to be significantly increased in SF compared with plasma samples of RA patients (p = 0.005). Increased levels of TRX in the SF of inflamed joints was found to be associated with RA when compared with other arthritides (p = 0.007). Restoration of GSH levels in SF T cells with N-acetyl-L-cysteine (NAC), enhanced mitogenic induced proliferative responses and IL-2 production. Collectively, these data impute an important role to an altered redox state in the hyporesponsiveness of joint T cells in patients with RA.

Redox-dependent structure and dynamics of macrophage migration inhibitory factor reveal sites of latent allostery

“…27 Further, the synovial fluid of rheumatoid arthritis patients has been shown to be highly oxidizing relative to that of a non-arthritic control group. 43,44 A significant body of literature suggests that when overexpressed at sites of inflammation, 16 MIF can endure large swings in environmental redox potential, consistent with our determination of the MIF redox potential in vitro using solution NMR 45,46 (Figure S12, midpoint 𝐸 " # = -215 ± 5 mV, near normal physiological range). NMR spin relaxation studies show redox-dependent modulation of local flexibility in MIF, with motion observed on multiple timescales.…”

Research progress and hot spot analysis related to oxidative stress and osteoarthritis: a bibliometric analysis

“…The first study published in this field was on the effect of redox status on rheumatoid arthritis published in 1997 [ 29 ]. This study found that altered redox status had an important role in the hyporesponsiveness of joint T cells in patients with rheumatoid arthritis, revealing part of the mechanism by which oxidative stress causes rheumatoid arthritis.…”

Malabaricone C, a constituent of spice Myristica malabarica, exhibits anti-inflammatory effects via modulation of cellular redox

“…However, under specific pathological conditions like autoimmunity, allergy, chronic inflammation, COVID-19, and acute GvHD, there is a need to suppress T-cell activation (Maurice et al . 1997 ; Griffiths et al . 2011 ; Weyand et al .…”