scholarly journals Excessive Reactive Oxygen Species Inhibit IL-17A+ γδ T Cells and Innate Cellular Responses to Bacterial Lung Infection

2020 ◽  
Vol 32 (13) ◽  
pp. 943-956
Author(s):  
Desiree Anthony ◽  
Angelica Papanicolaou ◽  
Hao Wang ◽  
Huei Jiunn Seow ◽  
Eunice E. To ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
T Cells ◽  
Reactive Oxygen ◽  
Γδ T Cells ◽  
Cellular Responses ◽  
Lung Infection ◽  
Oxygen Species

scholarly journals Induction of regulatory T cells by macrophages is dependent on production of reactive oxygen species

2010 ◽  
Vol 107 (41) ◽  
pp. 17686-17691 ◽  
Author(s):  
Marina D. Kraaij ◽  
Nigel D. L. Savage ◽  
Sandra W. van der Kooij ◽  
Karin Koekkoek ◽  
Jun Wang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
T Cells ◽  
Regulatory T Cells ◽  
Reactive Oxygen ◽  
Oxygen Species

scholarly journals AToxoplasmaProlyl Hydroxylase Mediates Oxygen Stress Responses by Regulating Translation Elongation

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Celia Florimond ◽  
Charlotte Cordonnier ◽  
Rahil Taujale ◽  
Hanke van der Wel ◽  
Natarajan Kannan ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Protein Synthesis ◽  
Toxoplasma Gondii ◽  
Oxygen Sensing ◽  
Reactive Oxygen ◽  
Protozoan Parasite ◽  
Cellular Responses ◽  
Parasite Growth ◽  
Oxygen Species ◽  
Prolyl Hydroxylases

ABSTRACTAs the protozoan parasiteToxoplasma gondiidisseminates through its host, it responds to environmental changes by altering its gene expression, metabolism, and other processes. Oxygen is one variable environmental factor, and properly adapting to changes in oxygen levels is critical to prevent the accumulation of reactive oxygen species and other cytotoxic factors. Thus, oxygen-sensing proteins are important, and among these, 2-oxoglutarate-dependent prolyl hydroxylases are highly conserved throughout evolution.Toxoplasmaexpresses two such enzymes, TgPHYa, which regulates the SCF-ubiquitin ligase complex, and TgPHYb. To characterize TgPHYb, we created aToxoplasmastrain that conditionally expresses TgPHYb and report that TgPHYb is required for optimal parasite growth under normal growth conditions. However, exposing TgPHYb-depleted parasites to extracellular stress leads to severe decreases in parasite invasion, which is likely due to decreased abundance of parasite adhesins. Adhesin protein abundance is reduced in TgPHYb-depleted parasites as a result of inactivation of the protein synthesis elongation factor eEF2 that is accompanied by decreased rates of translational elongation. In contrast to most other oxygen-sensing proteins that mediate cellular responses to low O2, TgPHYb is specifically required for parasite growth and protein synthesis at high, but not low, O2tensions as well as resistance to reactive oxygen species.In vivo, reduced TgPHYb expression leads to lower parasite burdens in oxygen-rich tissues. Taken together, these data identify TgPHYb as a sensor of high O2levels, in contrast to TgPHYa, which supports the parasite at low O2.IMPORTANCEBecause oxygen plays a key role in the growth of many organisms, cells must know how much oxygen is available. O2-sensing proteins are therefore critical cellular factors, and prolyl hydroxylases are the best-studied type of O2-sensing proteins. In general, prolyl hydroxylases trigger cellular responses to decreased oxygen availability. But, how does a cell react to high levels of oxygen? Using the protozoan parasiteToxoplasma gondii, we discovered a prolyl hydroxylase that allows the parasite to grow at elevated oxygen levels and does so by regulating protein synthesis. Loss of this enzyme also reduces parasite burden in oxygen-rich tissues, indicating that sensing both high and low levels of oxygen impacts the growth and physiology ofToxoplasma.

Involvement of T cells and the reactive oxygen species in patients with allergic reaction to drugs

2003 ◽  
Vol 111 (2) ◽  
pp. S169
Author(s):  
J.A. Cornejo-Garcia ◽  
M.J. Torres ◽  
C. Mayorga ◽  
C. Antunez ◽  
T. Bellon ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
T Cells ◽  
Allergic Reaction ◽  
Reactive Oxygen ◽  
Oxygen Species

Reactive oxygen species induce signals that lead to apoptotic DNA degradation in primary CD4+ T cells

APOPTOSIS ◽  
2005 ◽  
Vol 10 (6) ◽  
pp. 1433-1443 ◽  
Author(s):  
M. Pajusto ◽  
T. H. Toivonen ◽  
J. Tarkkanen ◽  
E. Jokitalo ◽  
P. S. Mattila
Keyword(s):  
Reactive Oxygen Species ◽  
T Cells ◽  
Cd4 T Cells ◽  
Reactive Oxygen ◽  
Dna Degradation ◽  
Oxygen Species

scholarly journals Melatonin, an Endogenous Hormone, Modulates Th17 Cells via the Reactive Oxygen Species/TXNIP/HIF-1α Axis to Alleviate Autoimmune Uveitis

2022 ◽  
Author(s):  
Dan Liang ◽  
Jun Huang ◽  
Zhuang Li ◽  
Yunwei Hu ◽  
Zuoyi Li ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Flow Cytometry ◽  
T Cells ◽  
Th17 Cells ◽  
Reactive Oxygen ◽  
Treg Cells ◽  
Oxygen Species ◽  
T Helper ◽  
Autoimmune Uveitis

Abstract Background Melatonin, an indoleamine produced by the pineal gland, plays a pivotal role in maintaining circadian rhythm homeostasis. Recently, the strong antioxidant and anti-inflammatory properties of melatonin have attracted attention of researchers. We evaluated the therapeutic efficacy of melatonin in experimental autoimmune uveitis (EAU), which is a representative animal model of human autoimmune uveitis. Methods EAU was induced in mice via immunization with the peptide interphotoreceptor retinoid binding protein 1-20 (IRBP1−20). melatonin was then administered via intraperitoneal injection to induce protection against EAU. With EAU induction for 14 days, clinical and histopathological scores were employed to evaluate the disease progression. T lymphocytes accumulation, the expression of inflammatory cytokines in the retinas were assessed via flow cytometry and RT-PCR. In vivo and in vitro experiments, T helper 1 (Th1), T helper 17 (Th17) and regulatory T (Treg) cells were detected via flow cytometry, the level reactive oxygen species(ROS) from CD4+ cells were tested via flow cytometry, and the expression of thioredoxin-interacting protein (TXNIP) and hypoxia-inducible factor 1 alpha (HIF-1α)proteins were also quantified via western blot analysis, to elucidate the mechanism of melatonin inhibiting EAU. Results Melatonin treatment resulted in notable attenuation of ocular inflammation in EAU mice, evidenced by decreasing optic disc edema, few signs of retinal vasculitis, and minimal retinal and choroidal infiltrates. Mechanistic studies revealed that melatonin restricted the proliferation of peripheral Th1 and Th17 cells and potentiated Treg cells by suppressing their transcription factors. In vitro studies corroborated that melatonin restrains the polarization of retina-specific T cells towards Th17 and Th1 cells in addition to enhancing the proportion of Treg cells. Pretreatment of retina-specific T cells with melatonin failed to induce EAU in naïve recipients. Furthermore, the ROS/ TXNIP/ HIF-1α pathway was shown to mediate the therapeutic effect of melatonin in EAU. Conclusions Melatonin regulates autoimmune T cells by restraining effector T cells and facilitating Treg generation, indicating that melatonin could be a hopeful treatment alternative for autoimmune uveitis.

Contrasting Requirement for Reactive Oxygen Species for the Suppressive Function of Naturally Occurring Regulatory T Cells but Not Induced Regulatory T Cells.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2146-2146
Author(s):  
Todd W. Kelley ◽  
Olga Efimova ◽  
Jonathan Schumacher ◽  
Philippe Szankasi
Keyword(s):  
Reactive Oxygen Species ◽  
T Cells ◽  
Regulatory T Cells ◽  
Nadph Oxidase ◽  
Reactive Oxygen ◽  
Related Factor ◽  
Oxygen Species ◽  
Tgf Beta ◽  
Suppressive Function ◽  
Naturally Occurring

Abstract Abstract 2146 Background: Naturally-occurring, thymus-derived regulatory T cells (nTregs) have clinically important roles in suppression of autoimmunity and graft versus host disease but are maladaptive in the tumor microenvironment where their activity results in the suppression of anti-tumor immunity. Induced regulatory T cells (iTregs) arise in the periphery under the influence of TGF-beta and have related phenotypic features and function. However, the mechanisms by which nTregs and iTregs impart suppression remain poorly understood. We have previously shown that NADPH oxidase derived reactive oxygen species (ROS) are important for nTreg suppressive function. We extend these observations and find distinct differences in the effect of antioxidants and NADPH oxidase inhibitors on blocking nTreg function but not iTreg function thus implying a role for ROS in the function of the former but not the latter. The contrasting requirement for ROS is further supported by distinct differences in expression of oxidant related genes in nTregs and iTregs. Methods: Murine nTregs were isolated by flow cytometric sorting for CD4+CD25++ T cells. Murine iTregs were induced from spleen sorted naïve T cells (CD4+CD44-) by incubating with TGF-beta and IL-2 and the resulting cells were sorted for the CD25++ subset. For suppression assays, nTregs and iTregs were incubated for three days with CFSE-labeled conventional T cells (Tc; CD4+CD25−) with antioxidants or NADPH oxidase inhibitors, as indicated. The proliferation of Tc co-incubated with Tregs was compared to their proliferation in identical conditions lacking Tregs in classical suppression assays. In some cases, nTregs and iTregs were co-incubated with CFSE-labeled Tc for two days in conditions identical to suppression assays to activate their suppressive function then resorted and subjected to RNA extraction and analysis of mRNA expression of a series of oxidant related genes. Results and Discussion: The antioxidants n-acetylcysteine (NAC; 1mM) and beta-mercaptoethanol (B-ME; 50 uM) had only small effects on suppression imparted by iTregs (p<0.01) while they completely blocked suppression by nTregs (see figure; p<0.0001). NADPH oxidase inhibitors VAS2870 (100nM) and diphenyleneiodonium (DPI; 10nM) demonstrated only mild effects on suppression by iTregs (p<0.01) while markedly reducing suppression by nTregs (p<0.001; see figure). iTregs derived from mice lacking a functional NADPH oxidase complex due to a mutation in the NADPH oxidase subunit NCF1 (NCF1−/−) demonstrated suppressive activity that was similar to wild type (NCF+/+) iTregs, thus genetically confirming no role for NADPH oxidase derived ROS for iTreg-mediated suppression. To evaluate dynamic functional differences between nTregs and iTregs, the expression of a series of ROS related genes was analyzed in purified Tregs with activated suppressive function. This demonstrated overexpression of two genes involved in oxidant detoxification in nTregs: sulfiredoxin1 (SRXN1; >16 fold overexpression in nTregs vs iTregs; mean of 3 experiments) and glutathione peroxidase 3 (GPX3; approximately 3-fold overexpression in nTregs vs iTregs; mean of 3 experiments). Overexpression of SRXN1 and GPX3 in nTregs was confirmed with additional unrelated assays. SRXN1 is a transcriptional target for the cytoprotective transcription factor nuclear factor erythroid 2-related factor 2 (NRF2). Therefore, we separately evaluated NRF2 expression and found approximately 2.5-fold mean overexpression in nTregs vs iTregs. Thus, because ROS is an important mediator of nTreg suppressive function we hypothesize that activation of NRF2, and downstream antioxidants such as SRXN1, are critical for the oxidant protection of nTregs themselves during suppression. Conclusions: Our findings illustrate fundamental differences in suppressive mechanisms employed by murine nTregs and iTregs and highlight a role for ROS in the former but not the latter. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document