The Interaction of Sodium and Zinc in the Priming of T Cell Subpopulations Regarding Th17 and Treg Cells

Abstract Context Regulatory T (Treg) cells and T-helper-17 (Th17) cells may be involved in endometriosis. Information on the pattern of change in the percentages of Treg and Th17 cells in the peripheral blood (PB) and peritoneal fluid (PF) of women with early and advanced endometriosis is unclear. Objective To investigate the pattern of change in the percentages of Treg and Th17 cells in the PB and PF of women with early and advanced endometriosis. Methods We recruited 31 women with laparoscopically and histologically confirmed, revised American Society of Reproductive Medicine stage I-II endometriosis, 39 women with stage III-IV endometriosis, and 36 control subjects without visible endometriosis. PB and PF samples were collected and T-cell subpopulations analyzed by flow cytometry using specific monoclonal antibodies recognizing CD4+, CD25+, FOXP3+, and IL-17A+ markers. PF concentrations of TGF-β and IL-17 were measured by ELISA. Results The percentages of CD25+FOXP3+ Treg cells within the CD4+ T-cell population were significantly higher in the PF of women with advanced endometriosis than in either early endometriosis or in control subjects (P < 0.05 for both). A persistently lower percentage of CD4+IL-17A+ Th17 cells was found in both PB and PF of women with early and advanced endometriosis. Compared with IL-17 levels, PF levels of TGF-β were significantly higher in women with endometriosis (P = 0.01). Conclusion Our findings reconfirmed the current speculation that endometriosis is related to alteration of Treg and Th17 cells in the pelvis causing survival and implantation of ectopic endometrial lesions.

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Low-dose decitabine modulates T cell homeostasis and restores immune tolerance in immune thrombocytopenia

Blood ◽

10.1182/blood.2020008477 ◽

2021 ◽

Author(s):

Panpan Han ◽

Yu Hou ◽

Yajing Zhao ◽

Yang Liu ◽

Yunqi Sun ◽

...

Keyword(s):

T Cell ◽

Immune Tolerance ◽

Immune Thrombocytopenia ◽

Low Dose ◽

Treg Cells ◽

T Cell Homeostasis ◽

Cell Homeostasis ◽

Cytokine Analysis ◽

Cell Subpopulations ◽

T Cell Subpopulations

Our previous clinical study demonstrated that low-dose decitabine showed sustained responses in nearly half of refractory immune thrombocytopenia (ITP) patients. The long-term efficacy of decitabine in ITP is not likely due to its simple role in increasing platelet production. Whether decitabine has the potential to restore immune tolerance in ITP is unknown. In this study, we analyzed the effect of decitabine on T cell subpopulations in ITP in vitro and in vivo. We found that low-dose decitabine promoted the generation and differentiation of regulatory T (Treg) cells, and augmented their immunosuppressive function. Splenocytes from CD61 knockout mice immunized with CD61+ platelets were transferred into severe combined immunodeficient (SCID) mouse recipients to induce a murine model of ITP. Low-dose decitabine alleviated thrombocytopenia and restored the balance between Treg and helper T (Th) cells in active ITP mice. Treg deletion and depletion offset the effect of decitabine in restoring CD4+ T cell subpopulations in ITP mice. For patients who received low-dose decitabine, the quantity and function of Treg cells were substantially improved, whereas Th1 and Th17 cells were suppressed compared with the pretreatment levels. Next-generation RNA sequencing and cytokine analysis showed that low-dose decitabine rebalanced T cell homeostasis, decreased proinflammatory cytokines, and down-regulated phosphorylated STAT3 in ITP patients. STAT3 inhibition analysis suggested that low-dose decitabine might restore Treg cells by inhibiting STAT3 activation. In conclusion, our data indicated that the immunomodulatory effect of decitabine provided one possible mechanistic explanation for the sustained response achieved by low-dose decitabine in ITP.

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Decreased numbers and sex-based differences of circulating regulatory T cells in patients with seropositive undifferentiated arthritis

Therapeutic Advances in Chronic Disease ◽

10.1177/2040622320986721 ◽

2021 ◽

Vol 12 ◽

pp. 204062232098672

Author(s):

Hong-Qing Niu ◽

Chenrui Yuan ◽

Chenglan Yan ◽

Na Li ◽

Yuan-Sheng Lei ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Flow Cytometric Analysis ◽

Treg Cells ◽

T Cell Subsets ◽

Joint Disease ◽

Healthy Controls ◽

Undifferentiated Arthritis ◽

Cell Subpopulations ◽

T Cell Subpopulations

Aims: CD4+ T cells play crucial roles as both mediators and regulators of the pathogenesis of rheumatoid arthritis (RA). However, the characteristics of CD4+ T cell subpopulations in the earliest stage of RA development remain unclear. Hence, we determined the proportions and absolute counts of circulating CD4+ T cell subsets in patients with seropositive undifferentiated arthritis (SUA), the early and preclinical stage of RA. Methods: Peripheral blood samples and clinical information were collected from 177 patients with SUA, 104 patients with RA, and 120 healthy controls. All patients were newly diagnosed and untreated. Proportions and absolute counts of CD4+ T cell subpopulations were determined by flow cytometric analysis. Results: In patients with SUA, percentages and absolute counts of circulating regulatory T (Treg) cells were decreased significantly and Th17/Treg cell ratios were abnormally increased, whereas Th17 cell numbers were similar to those in healthy controls. In addition, sex-based differences in circulating Treg cells were observed, with female SUA patients having lower proportions and absolute counts of Treg cells than those in males. Moreover, female patients with SUA had higher erythrocyte sedimentation rates and 28-joint Disease Activity Scores than those in males. Conclusion: Immune tolerance deficiency resulting from an abnormal reduction in circulating Treg cells might be the most crucial immunological event in the earliest stage of RA. The sex-specific disparity in Treg cells should also be considered for immunoregulatory and preventive strategies targeting early RA.

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Regulatory T Cell-Enhancing Therapies to Treat Atherosclerosis

Cells ◽

10.3390/cells10040723 ◽

2021 ◽

Vol 10 (4) ◽

pp. 723

Author(s):

Hafid Ait-Oufella ◽

Jean-Rémi Lavillegrand ◽

Alain Tedgui

Keyword(s):

T Cell ◽

Current Knowledge ◽

Experimental Studies ◽

Therapeutic Approaches ◽

Coronary Patients ◽

Cell Subpopulations ◽

Atherosclerotic Process ◽

T Cell Subpopulations ◽

Disease Analysis

Experimental studies have provided strong evidence that chronic inflammation triggered by the sub-endothelial accumulation of cholesterol-rich lipoproteins in arteries is essential in the initiation and progression of atherosclerosis. Recent clinical trials highlighting the efficacy of anti-inflammatory therapies in coronary patients have confirmed that this is also true in humans Monocytes/macrophages are central cells in the atherosclerotic process, but adaptive immunity, through B and T lymphocytes, as well as dendritic cells, also modulates the progression of the disease. Analysis of the role of different T cell subpopulations in murine models of atherosclerosis identified effector Th1 cells as proatherogenic, whereas regulatory T cells (Tregs) have been shown to protect against atherosclerosis. For these reasons, better understanding of how Tregs influence the atherosclerotic process is believed to provide novel Treg-targeted therapies to combat atherosclerosis. This review article summarizes current knowledge about the role of Tregs in atherosclerosis and discusses ways to enhance their function as novel immunomodulatory therapeutic approaches against cardiovascular disease.

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Adult Renal Stem/Progenitor Cells Can Modulate T Regulatory Cells and Double Negative T Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22010274 ◽

2020 ◽

Vol 22 (1) ◽

pp. 274

Author(s):

Claudia Curci ◽

Angela Picerno ◽

Nada Chaoul ◽

Alessandra Stasi ◽

Giuseppe De Palma ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Progenitor Cells ◽

Mononuclear Cells ◽

Human Peripheral Blood ◽

Double Negative ◽

Chronic Injury ◽

Peripheral Blood Mononuclear ◽

Cell Subpopulations ◽

T Cell Subpopulations

Adult Renal Stem/Progenitor Cells (ARPCs) have been recently identified in the human kidney and several studies show their active role in kidney repair processes during acute or chronic injury. However, little is known about their immunomodulatory properties and their capacity to regulate specific T cell subpopulations. We co-cultured ARPCs activated by triggering Toll-Like Receptor 2 (TLR2) with human peripheral blood mononuclear cells for 5 days and 15 days and studied their immunomodulatory capacity on T cell subpopulations. We found that activated-ARPCs were able to decrease T cell proliferation but did not affect CD8+ and CD4+ T cells. Instead, Tregs and CD3+ CD4- CD8- double-negative (DN) T cells decreased after 5 days and increased after 15 days of co-culture. In addition, we found that PAI1, MCP1, GM-CSF, and CXCL1 were significantly expressed by TLR2-activated ARPCs alone and were up-regulated in T cells co-cultured with activated ARPCs. The exogenous cocktail of cytokines was able to reproduce the immunomodulatory effects of the co-culture with activated ARPCs. These data showed that ARPCs can regulate immune response by inducing Tregs and DN T cells cell modulation, which are involved in the balance between immune tolerance and autoimmunity.

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T-cell subpopulations and colorectal cancer

Diseases of the Colon & Rectum ◽

10.1007/bf02156259 ◽

1990 ◽

Vol 33 (5) ◽

pp. 367-369

Author(s):

Andrea Ferrara ◽

Marvin M. McMillen ◽

Garth H. Ballantyne

Keyword(s):

Colorectal Cancer ◽

T Cell ◽

Cell Subpopulations ◽

T Cell Subpopulations

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A Micromethod for the Detection of TG and TM Cells. Technical Aspects for the Enumeration of Human T-Cell Subpopulations

International Archives of Allergy and Immunology ◽

10.1159/000233100 ◽

1982 ◽

Vol 68 (3) ◽

pp. 214-218 ◽

Cited By ~ 1

Author(s):

J.R. Jensen

Keyword(s):

T Cell ◽

Technical Aspects ◽

Human T Cell ◽

Cell Subpopulations ◽

T Cell Subpopulations

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Distribution of T-cell subpopulations in the peripheral blood of patients with erythrodermic psoriasis

Archives of Dermatological Research ◽

10.1007/bf00406476 ◽

1984 ◽

Vol 277 (1) ◽

pp. 19-23 ◽

Cited By ~ 3

Author(s):

R. Willemze ◽

W. J. M. Damsteeg ◽

C. J. L. M. Meijer

Keyword(s):

T Cell ◽

Peripheral Blood ◽

Erythrodermic Psoriasis ◽

Cell Subpopulations ◽

T Cell Subpopulations

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Disproportion in T-cell subpopulations in immunodeficient mutant hr/hr mice.

Journal of Experimental Medicine ◽

10.1084/jem.149.1.228 ◽

1979 ◽

Vol 149 (1) ◽

pp. 228-233 ◽

Cited By ~ 22

Author(s):

A B Reske-Kunz ◽

M P Scheid ◽

E A Boyse

Keyword(s):

T Cells ◽

T Cell ◽

B Cells ◽

Lymph Nodes ◽

Salient Feature ◽

Mutant Gene ◽

Cell Subpopulations ◽

T Cell Subpopulations

Mice of the HRS strain, which carry the mutant gene hr, were examined for abnormalities in representation of the three T-cell sets Ly1, Ly23, and Ly123 in the spleen. The salient feature of hr/hr mice, which are immunologically deficient, in comparison with +/hr segregants, was a gross disproportion in numbers of cells belonging to the Ly1 and Ly123 sets, at the age of 3--3.5 mo. At this age, Ly123 cells of hr/hr spleen outnumbered Ly1 cells by 2:1, whereas in +/hr spleens Ly123 cells were outnumbered by approximately 1:2. Cells from pooled lymph nodes of hr/hr mice did not show a correspondingly gross disporprotion of Ly1 and Ly123 cells. Total counts of splenic T cells, and of B cells, were not significantly different in hr/hr and +/hr mice.

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