Impact of Nrf2 expression in reconstituting T-cells of allogeneic hematopoietic stem cell transplanted patients

Karl, Franziska; Stoll, Andrew L.; Böttcher-Loschinski, Romy; Böttcher, Martin; Baur, Rebecca; Jacobs, Bénédikt; Völkl, Simon; Jitschin, Regina; Rösler, Wolf; Mackensen, Andréas; Mougiakakos, Dimitrios

doi:10.1038/s41375-020-0956-0

Cited by 7 publications

(5 citation statements)

References 18 publications

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“…Several studies thus far have substantiated the protective role of Nrf2 in attenuating inflammation-driven pathology via controlling the expression of antioxidant and cell protective enzymes. For instance, studies on allogenic hematopoietic stem cell transplanted patients indicate that high expression of Nrf2 in cytotoxic CD8 + T-cells might be protective against graft-versus-host disease [ 54 ]. Also, a study on patients with childhood rheumatism (JIA) showed that Nrf2 activation of helper T cells (CD4 + T cells) downregulated oxidative stress markers, altered the metabolic phenotype and reduced secretion of IFNγ [ 55 ].…”

Section: Nrf2 Signaling and Its Role In Modulating Immune Responses T...mentioning

confidence: 99%

Regulation of immunomodulatory networks by Nrf2-activation in immune cells: Redox control and therapeutic potential in inflammatory diseases

Pant,

Uche,

Juric

et al. 2024

Redox Biology

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Section: Nrf2 Signaling and Its Role In Modulating Immune Responses T...mentioning

confidence: 99%

Regulation of immunomodulatory networks by Nrf2-activation in immune cells: Redox control and therapeutic potential in inflammatory diseases

Pant,

Uche,

Juric

et al. 2024

Redox Biology

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“…23 These shared TFs included activator protein 1 TFs (FOS/JUN), REL from the NF-κB family, as well as CREM and NFE2L2/NRF2, which have been linked to an immunosuppressive tumor microenvironment and CD8 + exhaustion, respectively. 24,25 TBX21 was the only TF whose regulon was enriched among the genes upregulated in CR CD8 + cells and contained mostly effectorassociated genes (Figure 3B).…”

Section: Cd8 + T Cells In Patients In Cr Are Characterized By High Ex...mentioning

confidence: 99%

The remission status of AML patients after allo-HCT is associated with a distinct single-cell bone marrow T-cell signature

Mathioudaki,

Wang,

Sedloev

et al. 2024

Blood

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Acute myeloid leukemia (AML) is a hematologic malignancy for which allogeneic stem cell transplantation (alloSCT) often remains the only curative therapeutic approach. However, incapability of T cells to recognize and eliminate residual leukemia stem cells (LSCs) might lead to an insufficient graft-versus-leukemia (GvL) effect and relapse. Here, we performed single-cell RNA-sequencing on bone marrow (BM) T lymphocytes and CD34+ cells of six AML patients 100 days after alloSCT to identify T cell signatures associated with either imminent relapse (REL) or durable complete remission (CR). We observed a higher frequency of cytotoxic CD8+ effector and gamma delta (γδ) T cells in CR versus REL samples. Pseudotime and gene regulatory network analyses revealed that CR CD8+ T cells were more advanced in maturation and had a stronger cytotoxicity signature, while REL samples were characterized by inflammatory TNF/NF-κB signaling and an immunosuppressive milieu. We identified ADGRG1/GPR56 as a surface marker enriched in CR CD8+ T cells and confirmed in a CD33-directed chimeric antigen receptor (CAR)-T/AML co-culture model that GPR56 becomes upregulated on T cells upon antigen encounter and elimination of AML cells. We show that GPR56 continuously increases at the protein level on CD8+ T cells after alloSCT and confirm faster IFNγ secretion upon re-exposure to matched, but not unmatched recipient AML cells in the GPR56+ versus GPR56- CD8+ T cell fraction. Together, our data provide a single-cell reference map of BM-derived T cells post alloSCT and propose GPR56 expression dynamics as a surrogate for antigen encounter post alloSCT.

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“…However constitutive ablation of NRF2 in T cells ameliorated graft-vs-host disease (GvHD) (46). Again, a study with human cells indicates that high expression of NRF2 in CD8 + T-cells might be protective against chronic GvHD (48). The role of oxidative stress in T regs is controversely discussed.…”

Section: Nrf2 and Redox Metabolism In T Cellsmentioning

confidence: 99%

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

Ohl

Tenbrock

2021

Front. Immunol.

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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.

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Impact of Nrf2 expression in reconstituting T-cells of allogeneic hematopoietic stem cell transplanted patients

Cited by 7 publications

References 18 publications

Regulation of immunomodulatory networks by Nrf2-activation in immune cells: Redox control and therapeutic potential in inflammatory diseases

Regulation of immunomodulatory networks by Nrf2-activation in immune cells: Redox control and therapeutic potential in inflammatory diseases

The remission status of AML patients after allo-HCT is associated with a distinct single-cell bone marrow T-cell signature

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

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