scholarly journals Untargeted Metabolomic Profiling of the Correlation Between Prognosis Differences and PD-1 Expression in Sepsis: A Preliminary Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Y. Bu ◽  
H. Wang ◽  
X. Ma ◽  
C. Han ◽  
X. Jia ◽  
...  

Objectives: The mortality rate of sepsis remains very high. Metabolomic techniques are playing increasingly important roles in diagnosis and treatment in critical care medicine. The purpose of our research was to use untargeted metabolomics to identify and analyze the common differential metabolites among patients with sepsis with differences in their 7-day prognosis and blood PD-1 expression and analyze their correlations with environmental factors.Methods: Plasma samples from 18 patients with sepsis were analyzed by untargeted LC-MS metabolomics. Based on the 7-day prognoses of the sepsis patients or their levels of PD-1 expression on the surface of CD4+ T cells in the blood, we divided the patients into two groups. We used a combination of multidimensional and monodimensional methods for statistical analysis. At the same time, the Spearman correlation analysis method was used to analyze the correlation between the differential metabolites and inflammatory factors.Results: In the positive and negative ionization modes, 16 and 8 differential metabolites were obtained between the 7-day death and survival groups, respectively; 5 and 8 differential metabolites were obtained between the high PD-1 and low PD-1 groups, respectively. We identified three common differential metabolites from the two groups, namely, PC (P-18:0/14:0), 2-ethyl-2-hydroxybutyric acid and glyceraldehyde. Then, we analyzed the correlations between environmental factors and the common differences in metabolites. Among the identified metabolites, 2-ethyl-2-hydroxybutyric acid was positively correlated with the levels of IL-2 and lactic acid (Lac) (P < 0.01 and P < 0.05, respectively).Conclusions: These three metabolites were identified as common differential metabolites between the 7-day prognosis groups and the PD-1 expression level groups of sepsis patients. They may be involved in regulating the expression of PD-1 on the surface of CD4+ T cells through the action of related environmental factors such as IL-2 or Lac, which in turn affects the 7-day prognosis of sepsis patients.

2021 ◽  
Author(s):  
Dingxi Zhou ◽  
Mariana Borsa ◽  
Daniel J. Puleston ◽  
Susanne Zellner ◽  
Jesusa Capera ◽  
...  

CD4+ T cells orchestrate both humoral and cytotoxic immune responses. While it is known that CD4+ T cell proliferation relies on autophagy, direct identification of the autophagosomal cargo involved is still missing. Here, we created a transgenic mouse model, which, for the first time, enables us to directly map the proteinaceous content of autophagosomes in any primary cell by LC3 proximity labelling. IL-7Rα, a cytokine receptor mostly found in naive and memory T cells, was reproducibly detected in autophagosomes of activated CD4+ T cells. Consistently, CD4+ T cells lacking autophagy showed increased IL-7Rα surface expression, while no defect in internalisation was observed. Mechanistically, excessive surface IL-7Rα sequestrates the common gamma chain, impairing the IL-2R assembly and downstream signalling crucial for T cell proliferation. This study provides proof-of-principle that key autophagy substrates can be reliably identified with this model to help mechanistically unravel autophagy's contribution to healthy physiology and disease.


2006 ◽  
Vol 194 (11) ◽  
pp. 1609-1616 ◽  
Author(s):  
Rebecca B. Blank ◽  
Erika W. Lamb ◽  
Anna S. Tocheva ◽  
Emily T. Crow ◽  
K. C. Lim ◽  
...  
Keyword(s):  
T Cells ◽  

Hepatology ◽  
2005 ◽  
Vol 42 (2) ◽  
pp. 293-300 ◽  
Author(s):  
Steven C. Katz ◽  
Venu G. Pillarisetty ◽  
Joshua I. Bleier ◽  
T. Peter Kingham ◽  
Umer I. Chaudhry ◽  
...  

2005 ◽  
Vol 128 (4) ◽  
pp. 922-934 ◽  
Author(s):  
Yasuyuki Kai ◽  
Ichiro Takahashi ◽  
Hiromichi Ishikawa ◽  
Takachika Hiroi ◽  
Tsunekazu Mizushima ◽  
...  

2017 ◽  
Vol 35 (6) ◽  
pp. 1299-1303 ◽  
Author(s):  
Morena Scotece ◽  
Tamara Pérez ◽  
Javier Conde ◽  
Vanessa Abella ◽  
Veronica López ◽  
...  

Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 608
Author(s):  
Milica Lazarević ◽  
Giuseppe Battaglia ◽  
Bojan Jevtić ◽  
Neda Djedovic ◽  
Valeria Bruno ◽  
...  

The aim of this study was to examine the in vitro effects of the slow-releasing H2S donor GYY4137 on the immune cells involved in the pathogenesis of the central nervous system (CNS) autoimmune disease, multiple sclerosis (MS). GYY4137 specifically potentiated TGF-β expression and production in dendritic cells and significantly reduced IFN-γ and IL-17 production in the lymph node and spinal cord T cells obtained from mice immunized with CNS antigens. Both the proportion of FoxP3+ regulatory CD4+ T cells in the lymph node cells, and the percentage of IL-17+ CD4+ T cells in the spinal cord cells were reduced upon culturing with GYY4137. Interestingly, the peripheral blood mononuclear cells obtained from the MS patients had a lower expression of the H2S-producing enzyme, 3-mercaptopyruvate-sulfurtransferase (MPST), in comparison to those obtained from healthy donors. A significant inverse correlation between the expression of MPST and several pro-inflammatory factors was also observed. Further studies on the relevance of the observed results for the pathogenesis and therapy of MS are warranted.


F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 327 ◽  
Author(s):  
Aalia Bano ◽  
Alejandra Pera ◽  
Ahmad Almoukayed ◽  
Thomas H.S. Clarke ◽  
Sukaina Kirmani ◽  
...  

Immunosenescence is thought to contribute to the increase of autoimmune diseases in older people. Immunosenescence is often associated with the presence of an expanded population of CD4 T cells lacking expression of CD28 (CD28null). These highly cytotoxic CD4 T cells were isolated from disease-affected tissues in patients with rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, or other chronic inflammatory diseases and their numbers appeared to be linked to disease severity. However, we recently demonstrated that the common herpes virus, cytomegalovirus (CMV), not ageing, is the major driver of this subset of cytotoxic T cells. In this review, we discuss how CMV might potentiate and exacerbate autoimmune disease through the expansion of CD28null CD4 T cells.


Author(s):  
qisong Peng ◽  
guoyou Shi ◽  
hongxiang lu

Background: The importance of sST2 has been increasingly appreciated because of its associated with the development of heart failure and related diseases. Objective: The aim of this study was to evaluate the association of sST2 with CD4+T cells in patients with organ failure. Methods: 100 (M:F=60:40) organ failure patients aged (mean±SD=69.08±16.68) and 30 (M:F=14:16) normal control aged (mean±SD=60.23±13.99) serum sST2 were detected by chemiluminescence assay (CLIA) and the expression of serum IL-1, IL-6 and TNF-α were analyzed by enzyme-linked immunosorbent assay (ELISA). The proportion of CD4+T cells in peripheral blood was determined by flow cytometry (FCM). Association of sST2 with CD4+T cells in organ failure patents were analyzed by SPASS. Results: The expression of sST2 in organ failure patients (107.4±5.79ng/mL) was significantly higher than normal control (8.57±0.35ng/mL). Inflammatory factors IL-1 and IL-6 in patients were also increased than normal controls (IL-1: 0.33±0.04pg/mL vs 0.14±0.02pg/mL. IL-6: 165.7±10.53pg/mL vs 95.33±7.42pg/mL. TNF-α: 1.57±0.14pg/mL vs 6.11±0.77pg/mL). In patients, the results showed CD4+T cells were reduced compare with normal control (238.3±13.67/μL vs 1081±39.13/μL). Additionally, sST2 was found to be inversely associated with CD4+T cell in patients with organ failure. Conclusion: sST2 level was closely related to the development of organ failure and sST2 was obviously correlated with CD4+T cell in patients with organ failure.


2000 ◽  
Vol 164 (3) ◽  
pp. 1175-1184 ◽  
Author(s):  
Susanna Grundström ◽  
Mikael Dohlsten ◽  
Anette Sundstedt
Keyword(s):  
T Cells ◽  

1997 ◽  
Vol 185 (2) ◽  
pp. 189-196 ◽  
Author(s):  
Hiroshi Nakajima ◽  
Elizabeth W. Shores ◽  
Masayuki Noguchi ◽  
Warren J. Leonard

In the immune system, there is a careful regulation not only of lymphoid development and proliferation, but also of the fate of activated and proliferating cells. Although the manner in which these diverse events are coordinated is incompletely understood, cytokines are known to play major roles. Whereas IL-7 is essential for lymphoid development, IL-2 and IL-4 are vital for lymphocyte proliferation. The receptors for each of these cytokines contain the common cytokine receptor γ chain (γc), and it was previously shown that γc-deficient mice exhibit severely compromised development and responsiveness to IL-2, IL-4, and IL-7. Nevertheless, these mice exhibit an age-dependent accumulation of splenic CD4+ T cells, the majority of which have a phenotype typical of memory/activated cells. When γc-deficient mice were mated to DO11.10 T cell receptor (TCR) transgenic mice, only the T cells bearing endogenous TCRs had this phenotype, suggesting that its acquisition was TCR dependent. Not only do the CD4+ T cells from γc-deficient mice exhibit an activated phenotype and greatly enhanced incorporation of bromodeoxyuridine but, consistent with the lack of γc-dependent survival signals, they also exhibit an augmented rate of apoptosis. However, because the CD4+ T cells accumulate, it is clear that the rate of proliferation exceeds the rate of cell death. Thus, surprisingly, although γc-independent signals are sufficient to mediate expansion of CD4+ T cells in these mice, γc-dependent signals are required to regulate the fate of activated CD4+ T cells, underscoring the importance of γc-dependent signals in controlling lymphoid homeostasis.


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