scholarly journals Profound Treg perturbations correlate with COVID-19 severity

2020 ◽  
Author(s):  
Silvia Galvan-Pena ◽  
Juliette Leon ◽  
Kaitavjeet Chowdhary ◽  
Daniel A. Michelson ◽  
Brinda Vijaykumar ◽  
...  
Keyword(s):  
T Regulatory Cells ◽  
Severe Disease ◽  
Immune Homeostasis ◽  
Regulatory Cells ◽  
Cell Responses ◽  
Poor Outcomes ◽  
Inflammatory Molecules ◽  
Acute Patients ◽  
Treg Phenotype ◽  
Immunological Dysfunction

The hallmark of severe COVID-19 disease has been an uncontrolled inflammatory response, resulting from poorly understood immunological dysfunction. We explored the hypothesis that perturbations in FoxP3+ T regulatory cells (Treg), key enforcers of immune homeostasis, contribute to COVID-19 pathology. Cytometric and transcriptomic profiling revealed a distinct Treg phenotype in severe COVID-19 patients, with an increase in both Treg proportions and intracellular levels of the lineage-defining transcription factor FoxP3, which correlated with poor outcomes. Accordingly, these Tregs over-expressed a range of suppressive effectors, but also pro-inflammatory molecules like IL32. Most strikingly, they acquired similarity to tumor-infiltrating Tregs, known to suppress local anti-tumor responses. These traits were most marked in acute patients with severe disease, but persisted somewhat in convalescent patients. These results suggest that Tregs may play nefarious roles in COVID-19, via suppressing anti-viral T cell responses during the severe phase of the disease, and/or via a direct pro-inflammatory role.

scholarly journals Profound Treg perturbations correlate with COVID-19 severity

2021 ◽  
Vol 118 (37) ◽  
pp. e2111315118
Author(s):  
Silvia Galván-Peña ◽  
Juliette Leon ◽  
Kaitavjeet Chowdhary ◽  
Daniel A. Michelson ◽  
Brinda Vijaykumar ◽  
...  
Keyword(s):  
T Regulatory Cells ◽  
Severe Disease ◽  
Striking Similarity ◽  
Regulatory Cells ◽  
Transcriptional Signature ◽  
Cell Responses ◽  
Proinflammatory Role ◽  
Poor Outcomes ◽  
Treg Phenotype ◽  
Immunological Dysfunction

The hallmark of severe COVID-19 is an uncontrolled inflammatory response, resulting from poorly understood immunological dysfunction. We hypothesized that perturbations in FoxP3+ T regulatory cells (Treg), key enforcers of immune homeostasis, contribute to COVID-19 pathology. Cytometric and transcriptomic profiling revealed a distinct Treg phenotype in severe COVID-19 patients, with an increase in Treg proportions and intracellular levels of the lineage-defining transcription factor FoxP3, correlating with poor outcomes. These Tregs showed a distinct transcriptional signature, with overexpression of several suppressive effectors, but also proinflammatory molecules like interleukin (IL)-32, and a striking similarity to tumor-infiltrating Tregs that suppress antitumor responses. Most marked during acute severe disease, these traits persisted somewhat in convalescent patients. A screen for candidate agents revealed that IL-6 and IL-18 may individually contribute different facets of these COVID-19–linked perturbations. These results suggest that Tregs may play nefarious roles in COVID-19, by suppressing antiviral T cell responses during the severe phase of the disease, and by a direct proinflammatory role.

scholarly journals The Use of Probiotic Therapy to Modulate the Gut Microbiota and Dendritic Cell Responses in Inflammatory Bowel Diseases

2019 ◽  
Vol 7 (2) ◽  
pp. 33 ◽  
Author(s):  
Pablo Alagón Fernández del Campo ◽  
Alejandro De Orta Pando ◽  
Juan Ignacio Straface ◽  
José Ricardo López Vega ◽  
Diego Toledo Plata ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Inflammatory Bowel Diseases ◽  
T Regulatory Cells ◽  
Oxygen Species ◽  
Regulatory Cells ◽  
Population Status ◽  
Cell Responses ◽  
Bowel Diseases ◽  
Tolerance Response ◽  
Inflammatory Bowel

: Recent investigations have shown that different conditions such as diet, the overuse of antibiotics or the colonization of pathogenic microorganisms can alter the population status of the intestinal microbiota. This modification can produce a change from homeostasis to a condition known as imbalance or dysbiosis; however, the role-played by dysbiosis and the development of inflammatory bowel diseases (IBD) has been poorly understood. It was actually not until a few years ago that studies started to develop regarding the role that dendritic cells (DC) of intestinal mucosa play in the sensing of the gut microbiota population. The latest studies have focused on describing the DC modulation, specifically on tolerance response involving T regulatory cells or on the inflammatory response involving reactive oxygen species and tissue damage. Furthermore, the latest studies have also focused on the protective and restorative effect of the population of the gut microbiota given by probiotic therapy, targeting IBD and other intestinal pathologies. In the present work, the authors propose and summarize a recently studied complex axis of interaction between the population of the gut microbiota, the sensing of the DC and its modulation towards tolerance and inflammation, the development of IBD and the protective and restorative effect of probiotics on other intestinal pathologies.

scholarly journals The Coinhibitory Receptor CTLA-4 Controls B Cell Responses by Modulating T Follicular Helper, T Follicular Regulatory, and T Regulatory Cells

Immunity ◽  
2014 ◽  
Vol 41 (6) ◽  
pp. 1026-1039 ◽  
Author(s):  
Peter T. Sage ◽  
Alison M. Paterson ◽  
Scott B. Lovitch ◽  
Arlene H. Sharpe
Keyword(s):  
B Cell ◽  
T Regulatory Cells ◽  
Regulatory Cells ◽  
Cell Responses ◽  
Follicular Helper ◽  
B Cell Responses

scholarly journals CD8+ T regulatory cells in lupus

2021 ◽  
Vol 2 (3) ◽  
pp. 147-156
Author(s):  
Ram P. Singh ◽  
David S. Bischoff ◽  
Bevra H. Hahn
Keyword(s):  
Immune Tolerance ◽  
Lupus Erythematosus ◽  
T Regulatory Cells ◽  
Critical Role ◽  
Mechanisms Of Action ◽  
Immune Homeostasis ◽  
Regulatory Cells ◽  
Functional Deficits ◽  
Self Tolerance ◽  
Molecular Phenotypes

Abstract T regulatory cells (Tregs) have a key role in the maintenance of immune homeostasis and the regulation of immune tolerance by preventing the inflammation and suppressing the autoimmune responses. Numerical and functional deficits of these cells have been reported in systemic lupus erythematosus (SLE) patients and mouse models of SLE, where their imbalance and dysregulated activities have been reported to significantly influence the disease pathogenesis, progression and outcomes. Most studies in SLE have focused on CD4+ Tregs and it has become clear that a critical role in the control of immune tolerance after the breakdown of self-tolerance is provided by CD8+ Tregs. Here we review the role, cellular and molecular phenotypes, and mechanisms of action of CD8+ Tregs in SLE, including ways to induce these cells for immunotherapeutic modulation in SLE.

scholarly journals Hepatitis E rORF2p Stimulated and Unstimulated Peripheral Expression Profiling in Patients with Self-Limiting Hepatitis E Infection

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Sanjay B. Rathod ◽  
Anuradha S. Tripathy
Keyword(s):  
Gene Expression ◽  
Hepatitis E Virus ◽  
T Regulatory Cells ◽  
Current Knowledge ◽  
Expression Patterns ◽  
Hepatitis E ◽  
Fine Tuning ◽  
Regulatory Cells ◽  
Expression Array ◽  
Acute Patients

To improve the current knowledge on the involvement of peripheral lymphocytes in hepatitis E virus (HEV) associated pathogenesis, we analyzed alterations in (1) immunophenotypic expressions (by flow cytometry) and (2) gene expression patterns (by TaqMan Low Density Array) of activatory, inhibitory, integrin, homing, ectonucleotidase machinery, costimulatory, inflammatory markers, and T regulatory cells (Treg) associated cytokines on HEV rORF2p stimulated and unstimulated PBMCs of 43 acute HEV patients, 30 recovered individuals, and 43 controls. The phenotypic expressions of key molecules CTLA-4, GITR, CD103, CD25, CD69, IL10 and TGF-β1in the acute patients and TGF-β1in the recovered individuals were significantly elevated on both unstimulated and stimulated PBMCs. Gene expression array data revealed upregulations of CD25, PD1, CD103, CCR4, IL10, and TGF-β1on both unstimulated and HEV rORF2p stimulated PBMCs of acute patients. The observed upregulations of inhibitory, integrin, activatory, and Treg-associated cytokine genes on the PBMCs of acute HEV patients complemented by their frequency data suggest them as the major players in the fine-tuning of immune response in self-limiting hepatitis E infection.

Differential effect of CD4+Foxp3+ T-regulatory cells on the B and T helper cell responses to influenza virus vaccination

Vaccine ◽  
2010 ◽  
Vol 28 (45) ◽  
pp. 7319-7330 ◽  
Author(s):  
Jacqueline Surls ◽  
Cristina Nazarov-Stoica ◽  
Margaret Kehl ◽  
Sofia Casares ◽  
Teodor-D. Brumeanu
Keyword(s):  
Influenza Virus ◽  
Differential Effect ◽  
T Regulatory Cells ◽  
T Helper Cell ◽  
Helper Cell ◽  
Regulatory Cells ◽  
T Helper ◽  
Virus Vaccination ◽  
Cell Responses

scholarly journals T Regulatory Cells Contribute to the Attenuated Primary CD8+and CD4+T Cell Responses to Herpes Simplex Virus Type 2 in Neonatal Mice

2008 ◽  
Vol 180 (3) ◽  
pp. 1556-1564 ◽  
Author(s):  
Marian A. Fernandez ◽  
Franz K. Puttur ◽  
Yuan M. Wang ◽  
Wade Howden ◽  
Stephen I. Alexander ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
Herpes Simplex Virus Type ◽  
T Regulatory Cells ◽  
Cd4 T Cell ◽  
Regulatory Cells ◽  
Cell Responses ◽  
Simplex Virus

scholarly journals Plasmacytoid dendritic cells prime IL-10–producing T regulatory cells by inducible costimulator ligand

2007 ◽  
Vol 204 (1) ◽  
pp. 105-115 ◽  
Author(s):  
Tomoki Ito ◽  
Maria Yang ◽  
Yui-Hsi Wang ◽  
Roberto Lande ◽  
Josh Gregorio ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
T Regulatory Cells ◽  
Interleukin 10 ◽  
Regulatory Cells ◽  
Myeloid Dendritic Cells ◽  
Cell Responses ◽  
Inducible Costimulator ◽  
Th2 Differentiation

Although there is evidence for distinct roles of myeloid dendritic cells (DCs [mDCs]) and plasmacytoid pre-DCs (pDCs) in regulating T cell–mediated adaptive immunity, the concept of functional DC subsets has been questioned because of the lack of a molecular mechanism to explain these differences. In this study, we provide direct evidence that maturing mDCs and pDCs express different sets of molecules for T cell priming. Although both maturing mDCs and pDCs upregulate the expression of CD80 and CD86, only pDCs upregulate the expression of inducible costimulator ligand (ICOS-L) and maintain high expression levels upon differentiation into mature DCs. High ICOS-L expression endows maturing pDCs with the ability to induce the differentiation of naive CD4 T cells to produce interleukin-10 (IL-10) but not the T helper (Th)2 cytokines IL-4, -5, and -13. These IL-10–producing T cells are T regulatory cells, and their generation by ICOS-L is independent of pDC-driven Th1 and Th2 differentiation, although, in the later condition, some contribution from endogenous IL-4 cannot be completely ruled out. Thus, in contrast to mDCs, pDCs are poised to express ICOS-L upon maturation, which leads to the generation of IL-10–producing T regulatory cells. Our findings demonstrate that mDC and pDCs are intrinsically different in the expression of costimulatory molecules that drive distinct types of T cell responses.

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