The role of regulatory T cells in immune dysfunction during sepsis

Cao, Chao; Ma, Tao; Chai, Yifeng; Shou, Songtao

doi:10.5847/wjem.j.1920-8642.2015.01.001

Cited by 63 publications

(70 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Increased expression of pro‐apoptotic proteins such as Bax and cleaved caspase‐3 was detected in the LPS+ Fluoxetine group as compared to the LPS group and a simultaneous decrease in the anti‐apoptotic protein Bcl2 (Figure a). These changes were in accordance with previously described observations . These apoptotic changes were further evidenced by increased nuclear fragmentation in the thymocytes obtained from the fluoxetine‐supplemented LPS group as compared to the LPS‐only group (Figure b).…”

Section: Resultssupporting

confidence: 92%

“…There was a significant increase in the CD4 + :CD8 + ratio in the thymus and in the periphery, which was accompanied by a decrease in the number of CD4 + CD25 + (Treg) cells. Increase in the CD4 + /CD8 + ratio generally suggests the onset of a proliferative status in the immune system . Moreover, it has also been previously described that decrease in the %CD4 + CD25 + cells is an indication of the proliferation of the immune system .…”

Section: Discussionmentioning

confidence: 85%

“…In order to discern the probable bias within the cell types of the thymus that orchestrates this proliferative change, we analyzed the thymic CD4 + :CD8 + ratio, which is an essential marker for the determination of systemic immune suppression or proliferation status . LPS treatment induced significant increase in the CD4 + /CD8 + ratio with respect to the Control group (Figure c), whereas control thymus did not show any noticeable change in CD4 + /CD8 + ratio over the 3 weeks of experimental period (Figure c).…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, we observed in this study that sustained inflammation in the periphery could potentiate alterations in one of the major immune organs such as the thymus, as evident from increase in the thymic index. This critically suggests that, there are some deleterious effects within the thymus caused due to this inflammatory condition . Increased alterations in the thymic index led us to investigate the underlying cellular signaling pathways which could be involved in such changes.…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Fluoxetine triggers selective apoptosis in inflammation‐induced proliferating (Ki‐67^high) thymocytes

et al. 2019

View full text Add to dashboard Cite

Inappropriate functioning of the immune system is observed during sustained systemic inflammation, which might lead to immune deficiencies, autoimmune disorders and cancer. Primary lymphoid organs may progress to a deregulated proliferative state in response to inflammatory signals in order to intensify host defense mechanisms and exacerbate an inflammatory niche. Fluoxetine, a selective serotonin reuptake inhibitor, has recently been projected as an anti‐inflammatory agent. This study had been designed to evaluate the potential novel role of fluoxetine in reversing inflammation‐induced immune dysfunction. Lipopolysaccharide (LPS) administration in Swiss albino mice potentiated a systemic inflammatory response, along with increased proliferation of thymocytes and peripheral blood mononuclear cells, as evident from increased Ki‐67 expression. The proliferative changes in the immune system were mainly associated with increased phosphorylation of PI3k, AKT and IκB along with elevated NFκB‐p65 nuclear translocation. The Ki‐67high thymocytes obtained from LPS administered mice demonstrated significantly low p53 nuclear activity, which was established to be mediated by NFκB through reduced nuclear translocation of p53 during LPS‐induced proliferative conditions, thereby blocking p53‐dependent apoptosis. Fluoxetine supplementation not only reversed the proinflammatory condition, but also induced selective apoptosis in the proliferation‐dictated Ki‐67high thymocytes possibly by modulating the hypothalamus–pituitary–adrenal axis and inducing glucocorticoid receptor activation and apoptosis in these proliferation‐biased immune cells, authenticating a novel antiproliferative role of an established drug.

show abstract

Section: Resultssupporting

confidence: 92%

Section: Discussionmentioning

confidence: 85%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Fluoxetine triggers selective apoptosis in inflammation‐induced proliferating (Ki‐67^high) thymocytes

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Tregs are specialized immune cells that serve important roles in the maintenance of immune homeostasis (6). Tregs may contribute to immunosuppressive conditions during the course of sepsis, however, their relevance during early, delayed and recovery stages of the disease remain unclear and the results of previous studies are contradictory (7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Proteomic changes of CD4+/CD25+/forkhead box p3+ regulatory T cells in a 30‑day rat model of sepsis survival

2017

View full text Add to dashboard Cite

Abstract. Sepsis is defined as life threatening organ dysfunction arising from a dysregulated host response to infection. The outcomes of sepsis include early mortality, delayed mortality and recovery, and depend on the inflammatory response. Previous studies have demonstrated that regulatory T cells (Tregs) are important in determining the outcome of sepsis, as their suppressive function serves a role in maintaining immune homeostasis. However, Treg-mediated immunosuppression during the course of sepsis remains unclear and little is known about the survival of patients following diagnosis. Studying the survivors of sepsis may explain the mechanisms of natural recovery. Therefore, a 30-day rat model of sepsis survival was established in the current study. Cluster of differentiation CD4 + /CD25 + /forkhead box p3 + Tregs were isolated from the blood and spleens of rats undergoing cecal ligation and puncture or sham surgery, using flow cytometry. Proteomic analysis was performed using nano high-performance liquid chromatography -mass spectrometry. Several different biological pathways associated with uncommon differentially-expressed proteins were identified in the blood and spleen survivor and sham groups. Extracellular-regulated kinase/mitogen-activated protein kinase, as well as integrin and actin cytoskeletal pathway elements, including Ras-related protein 1b, talin 1 and filamin A, were associated with Tregs in the blood. Pathway elements associated with cell cycle regulators in the B-cell translocation gene family of proteins, tumor necrosis factor receptor superfamily member 4, Hippo signaling, P70-S6 kinase 1, phosphatidylinositol 3-kinase/protein kinase B signaling and 1,25-dihydroxyvitamin D3 biosynthesis were associated with Tregs from the spleen including phosphatase 2A activator regulatory factor 4, histone arginine methyltransferase, CD4, major histocompatibility complex class I antigens, 14-3-3 protein θ and nicotinamide adenine dinucleotide phosphate cytochrome P450 reductase. These results explain the mechanism by which Tregs naturally recover and indicates that Tregs in the blood and spleen vary. Differentially-expressed proteins serving a role in these pathways provide additional insight for the identification of new targets for the diagnosis and treatment of sepsis.

show abstract

Further study of circulating IgG antibodies to CD25‐derived peptide antigens in nonsmall cell lung cancer

et al. 2016

View full text Add to dashboard Cite

A recent study reported that circulating antibodies to CD25‐derived peptide antigens were significantly higher in patients with nonsmall cell lung cancer (NSCLC) than control subjects. The present study was, thus, undertaken to replicate the initial finding with different sample sets. An in‐house ELISA was applied to determine circulating IgG antibodies to linear peptide antigens derived from CD25. A total of 111 patients with NSCLC and 216 control subjects were recruited and divided into the discovery sample (51 vs 108) and the validation sample (60 vs 108) based on the time of sampling. Student's t test showed that circulating anti‐CD25 IgG levels were significantly higher in the patient group than the control group (t = 2.23, P = 0.027) and the validation sample replicated this finding (t = 3.31, P = 0.0012), generating a combined P value of 0.0004 (χ2 = 20.8, df = 4). Fisher's combining probability revealed that patients with stage IV NSCLC had a significant increase in anti‐CD25 IgG levels compared with control subjects (χ2 = 22.1, df = 4, P = 0.0002) but those with the other three stages did not. This study suggests that circulating anti‐CD25 IgG antibodies may have prognostic rather than early diagnostic values for lung cancer.

show abstract

The role of regulatory T cells in immune dysfunction during sepsis

Cited by 63 publications

References 29 publications

Fluoxetine triggers selective apoptosis in inflammation‐induced proliferating (Ki‐67^high) thymocytes

Fluoxetine triggers selective apoptosis in inflammation‐induced proliferating (Ki‐67^high) thymocytes

Proteomic changes of CD4+/CD25+/forkhead box p3+ regulatory T cells in a 30‑day rat model of sepsis survival

Further study of circulating IgG antibodies to CD25‐derived peptide antigens in nonsmall cell lung cancer

Contact Info

Product

Resources

About

The role of regulatory T cells in immune dysfunction during sepsis

Cited by 63 publications

References 29 publications

Fluoxetine triggers selective apoptosis in inflammation‐induced proliferating (Ki‐67high) thymocytes

Fluoxetine triggers selective apoptosis in inflammation‐induced proliferating (Ki‐67high) thymocytes

Proteomic changes of CD4+/CD25+/forkhead box p3+ regulatory T cells in a 30‑day rat model of sepsis survival

Further study of circulating IgG antibodies to CD25‐derived peptide antigens in nonsmall cell lung cancer

Contact Info

Product

Resources

About

Fluoxetine triggers selective apoptosis in inflammation‐induced proliferating (Ki‐67^high) thymocytes

Fluoxetine triggers selective apoptosis in inflammation‐induced proliferating (Ki‐67^high) thymocytes