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Review
. 2021 Apr 23:12:633845.
doi: 10.3389/fimmu.2021.633845. eCollection 2021.

Oxidative Stress in SLE T Cells, Is NRF2 Really the Target to Treat?

Kim Ohl  1 , Klaus Tenbrock  1
Affiliations
Review

Oxidative Stress in SLE T Cells, Is NRF2 Really the Target to Treat?

Kim Ohl et al. Front Immunol. .

Abstract

Oxidative stress is a major component of cellular damage in T cells from patients with systemic lupus erythematosus (SLE) resulting amongst others in the generation of pathogenic Th17 cells. The NRF2/Keap1 pathway is the most important antioxidant system protecting cells from damage due to oxidative stress. Activation of NRF2 therefore seems to represent a putative therapeutic target in SLE, which is nevertheless challenged by several findings suggesting tissue and cell specific differences in the effect of NRF2 expression. This review focusses on the current understanding of oxidative stress in SLE T cells and its pathophysiologic and therapeutic implications.

Keywords: Foxp3; Keap 1; ROS; Tregs; lupus; mTOR.

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Conflict of interest statement

The 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.

Figures

Figure 1
Figure 1
While systemic NRF2 activation can ameliorate pathogenesis, the exact role in T cells is not clear. (A) Oxidative stress is involved in SLE pathogenesis. Due to increased free radicals or a weak antioxidant system, SLE patients reveal high levels of oxidative stress which leads to cell damage and apoptosis. Subsequent release of autoantigens can enhance autoantibody formation and contribute to tissue damage. Tissue damage again can enhance oxidative stress. Several lines of evidence indicate that activated NRF2 can break the vicious circle by inducing anti-oxidative responses. (B) SLE T cell are hyper-oxidative. SLE T cells prefer the use of OXPHOS, which reduces NADPH and GSH pools, that are normally filled up during glycolysis and pentose phosphate pathway (PPP). In addition, they reveal a marked leakage of ROS during OXPHOS. High ROS levels induce mTOR activation. It is not clear, if NRF2 is not sufficiently activated or somehow fails to counteract high ROS levels in SLE T cells.
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