scholarly journals Immunological Mechanisms in Allergic Diseases and Allergen Tolerance: The Role of Treg Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
D. Calzada ◽  
S. Baos ◽  
L. Cremades-Jimeno ◽  
B. Cárdaba
Keyword(s):  
T Cells ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Public Health Problem ◽  
Allergic Diseases ◽  
Treg Cells ◽  
Cell Contact ◽  
Major Public Health Problem ◽  
Immunological Mechanisms

The immune system regulates itself to establish an appropriate immune response to potentially harmful pathogens while tolerating harmless environmental antigens and self-antigens. A central role in this balance is played by regulatory T cells (Tregs) through various ways of actions. By means of molecule secretion and cell-cell contact mechanisms, Tregs may have the capacity to modulate effector T cells and suppress the action of proinflammatory cytokines across a broad range of cell types. As a result, abnormal regulatory T cell function has been pointed as a main cause in the development of allergic diseases, a major public health problem in industrialized countries, with a high socioeconomic impact. This prevalence and impact have created an international interest in improving the allergy diagnosis and therapy. Additionally, research has sought to gain a better understanding of the molecular mechanisms underlining this kind of disease, in order to a better management. At this respect, the role of Treg cells is one of the most promising areas of research, mainly because of their potential use as new immunotherapeutical approaches. Therefore, the aim of this review is to update the existing knowledge of the role of Tregs in this pathology deepening in their implication in allergen-specific therapy (AIT).

scholarly journals The Relevance of MicroRNAs in the Pathogenesis and Prognosis of HCV-Disease: The Emergent Role of miR-17-92 in Cryoglobulinemic Vasculitis

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1364
Author(s):  
Serena Lorini ◽  
Laura Gragnani ◽  
Anna Linda Zignego
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Public Health Problem ◽  
Lymphoproliferative Disorders ◽  
Major Public Health Problem ◽  
Cryoglobulinemic Vasculitis ◽  
Association Analyses ◽  
Non Invasive

Hepatitis C virus (HCV) is a major public health problem. HCV is a hepatotropic and lymphotropic virus that leads to hepatocellular carcinoma (HCC) and lymphoproliferative disorders such as cryoglobulinemic vasculitis (CV) and non-Hodgkin’s lymphoma (NHL). The molecular mechanisms by which HCV induces these diseases are not fully understood. MicroRNAs (miRNAs) are small non-coding molecules that negatively regulate post-transcriptional gene expression by decreasing their target gene expression. We will attempt to summarize the current knowledge on the role of miRNAs in the HCV life cycle, HCV-related HCC, and lymphoproliferative disorders, focusing on both the functional effects of their deregulation as well as on their putative role as biomarkers, based on association analyses. We will also provide original new data regarding the miR 17-92 cluster in chronically infected HCV patients with and without lymphoproliferative disorders who underwent antiviral therapy. All of the cluster members were significantly upregulated in CV patients compared to patients without CV and significantly decreased in those who achieved vasculitis clinical remission after viral eradication. To conclude, miRNAs play an important role in HCV infection and related oncogenic processes, but their molecular pathways are not completely clear. In some cases, they may be potential therapeutic targets or non-invasive biomarkers of tumor progression.

scholarly journals Role of NLRP3 Inflammasome in the Progression of NAFLD to NASH

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Xingyong Wan ◽  
Chengfu Xu ◽  
Chaohui Yu ◽  
Youming Li
Keyword(s):  
Disease Progression ◽  
Nlrp3 Inflammasome ◽  
Interleukin 1 ◽  
Public Health Problem ◽  
Major Public Health Problem ◽  
Interleukin 1 Beta ◽  
Nonalcoholic Fatty Liver ◽  
Metabolic Inflammation ◽  
Immunological Mechanisms

Nonalcoholic fatty liver disease (NAFLD) has been recognized as a major public health problem worldwide. Nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD that may progress to cirrhosis and hepatocellular carcinoma. The pathogenesis of disease progression from NAFLD to NASH has not been fully understood. Immunological mechanisms that have been increasingly recognized in the disease progression include defects in innate immunity, adaptive immunity, Toll-like receptor (TLR) signaling, and gut-liver axis. The NLRP3 inflammasome is an intracellular multiprotein complex involved in the production of mature interleukin 1-beta (IL-1β) and induces metabolic inflammation. NLRP3 inflammasome has been recently demonstrated to play a crucial role in the progression of NASH. This review highlights the recent findings linking NLRP3 inflammasome to the progression of NASH.

scholarly journals Oxidative Imbalance and Kidney Damage: New Study Perspectives from Animal Models to Hospitalized Patients

Antioxidants ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 594 ◽  
Author(s):  
Daniela Pellegrino ◽  
Daniele La Russa ◽  
Alessandro Marrone
Keyword(s):  
Risk Factors ◽  
Animal Models ◽  
Molecular Mechanisms ◽  
Public Health Problem ◽  
Kidney Damage ◽  
Major Public Health Problem ◽  
Altered Expression ◽  
Oxidative Balance ◽  
Increased Risk

Chronic kidney disease (CKD) is a major public health problem worldwide and affects both elderly and young subjects. Its main consequences include the loss of renal function, leading to end-stage renal disease, an increased risk of cardiovascular disease, a significant increase in morbidity and mortality, and a decrease in health-related quality of life. This review arose in significant part from work in the authors’ laboratory, complemented by literature data, and was based on a translational approach: we studied the role of many CKD risk factors, such as hypertension, obesity, and oxidative stress/inflammation. The aim was to identify new molecular mechanisms of kidney damage to prevent it through successful behavior modifications. For this purpose, in our studies, both human and animal models were used. In the animal models, we analyzed the mechanisms of renal damage induced by hypertension (spontaneously hypertensive rats) and obesity (cafeteria diet-fed rats), showing that redox disequilibrium in plasma and tissue is extremely important in renal alteration in terms of both oxidative damage (lipid peroxidation, altered expression antioxidant enzymes) and apoptotic pathway (intrinsic/extrinsic) activation. In hemodialysis patients, we explored the correlation between the global oxidative balance and both inflammatory markers and cardiovascular risk, showing a strong correlation between the oxidative index and the blood levels of C-reactive protein and previous cardiovascular events. This multilevel approach allowed us to individually and synergistically analyze some aspects of the complex pathogenic mechanisms of CKD in order to clarify the role of the new amplified risk factors for CKD and to prepare an effective personalized prevention plan by acting on both modifiable and nonmodifiable risk factors.

Role of Regulatory T Cells in Infection and Vaccination During Early Infancy

2018 ◽  
Vol 24 (30) ◽  
pp. 3495-3505
Author(s):  
Samanta C. Funes ◽  
Miguel A. Mansilla ◽  
Gisela Canedo-Marroquín ◽  
Margarita K. Lay ◽  
Claudia A. Riedel ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Active Role ◽  
Treg Cells ◽  
Health Goals ◽  
Inhibitory Mechanisms ◽  
Neonates And Infants

Reducing infant mortality due to infectious diseases is one of the most important public health goals worldwide. Several approaches have been implemented to reach this goal and vaccination has been an effective strategy for reducing infant and newborn mortality. However, the immunological features of neonates and infants represent a significant barrier to the effectiveness of vaccination. Since regulatory T cells (Treg cells) are known to play an active role in contributing to various mechanisms of suppression of the immune cell function. It has been proposed that these immune cells could decrease the immunogenicity of vaccines administered in newborns and infants. In this article, we discuss the various types of Treg cells, along with their suppressing and inhibitory mechanisms, which are used by these cells in the context of infectious and immunization processes in newborns and infants.

Role of regulatory T-cells in autoimmunity

2009 ◽  
Vol 116 (8) ◽  
pp. 639-649 ◽  
Author(s):  
Richard J. Mellanby ◽  
David C. Thomas ◽  
Jonathan Lamb
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Treg Cell ◽  
Cell Function ◽  
Cell Subset ◽  
Treg Cells ◽  
Self Tolerance

There has been considerable historical interest in the concept of a specialist T-cell subset which suppresses over-zealous or inappropriate T-cell responses. However, it was not until the discovery that CD4+CD25+ T-cells had suppressive capabilities both in vitro and in vivo that this concept regained credibility and developed into one of the most active research areas in immunology today. The notion that in healthy individuals there is a subset of Treg-cells (regulatory T-cells) involved in ‘policing’ the immune system has led to the intensive exploration of the role of this subset in disease resulting in a number of studies concluding that a quantitative or qualitative decline in Treg-cells is an important part of the breakdown in self-tolerance leading to the development of autoimmune diseases. Although Treg-cells have subsequently been widely postulated to represent a potential immunotherapy option for patients with autoimmune disease, several studies of autoimmune disorders have demonstrated high numbers of Treg-cells in inflamed tissue. The present review highlights the need to consider a range of other factors which may be impairing Treg-cell function when considering the mechanisms involved in the breakdown of self-tolerance rather than focussing on intrinsic Treg-cell factors.

scholarly journals Enhancement of CD4+ T Cell Function as a Strategy for Improving Antibiotic Therapy Efficacy in Tuberculosis: Does It Work?

2021 ◽  
Vol 11 ◽  
Author(s):  
Diego L. Costa ◽  
Eduardo P. Amaral ◽  
Sivaranjani Namasivayam ◽  
Lara R. Mittereder ◽  
Bruno B. Andrade ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antibiotic Treatment ◽  
Cell Function ◽  
Public Health Problem ◽  
T Cell Responses ◽  
Effective Vaccine ◽  
Major Public Health Problem ◽  
Cell Responses ◽  
The Impact

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) remains a major public health problem worldwide due in part to the lack of an effective vaccine and to the lengthy course of antibiotic treatment required for successful cure. Combined immuno/chemotherapeutic intervention represents a major strategy for developing more effective therapies against this important pathogen. Because of the major role of CD4+ T cells in containing Mtb infection, augmentation of bacterial specific CD4+ T cell responses has been considered as an approach in achieving this aim. Here we present new data from our own research aimed at determining whether boosting CD4+ T cell responses can promote antibiotic clearance. In these studies, we first characterized the impact of antibiotic treatment of infected mice on Th1 responses to major Mtb antigens and then performed experiments aimed at sustaining CD4+ T cell responsiveness during antibiotic treatment. These included IL-12 infusion, immunization with ESAT-6 and Ag85B immunodominant peptides and adoptive transfer of Th1-polarized CD4+ T cells specific for ESAT-6 or Ag85B during the initial month of chemotherapy. These approaches failed to enhance antibiotic clearance of Mtb, indicating that boosting Th1 responses to immunogenic Mtb antigens highly expressed by actively dividing bacteria is not an effective strategy to be used in the initial phase of antibiotic treatment, perhaps because replicating organisms are the first to be eliminated by the drugs. These results are discussed in the context of previously published findings addressing this concept along with possible alternate approaches for harnessing Th1 immunity as an adjunct to chemotherapy.

scholarly journals Alcohol and fat promote steatohepatitis: a critical role for fat-specific protein 27/CIDEC

2016 ◽  
Vol 64 (6) ◽  
pp. 1078-1081 ◽  
Author(s):  
Suthat Liangpunsakul ◽  
Bin Gao
Keyword(s):  
Liver Disease ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Public Health Problem ◽  
Specific Protein ◽  
Major Public Health Problem ◽  
Therapeutic Benefits ◽  
New Concepts ◽  
End Stage

Alcoholic liver disease (ALD) is a major public health problem worldwide and is the leading cause of end-stage liver disease. While the ultimate control of ALD will require the prevention of alcohol abuse, better understanding of the mechanisms of alcohol-induced liver injury may lead to treatments of fatty liver, alcoholic hepatitis, and prevention or delay of occurrence of cirrhosis. The elucidation and the discovery of several new concepts in ALD pathogenesis have raised our understanding on the complex mechanisms and the potential in developing the new strategies for therapeutic benefits. In this review, we provide the most up-to-date information on the basic molecular mechanisms focusing on the role of fat-specific protein 27/CIDEC in the pathogenesis of ALD.

Dysfunctional T Regulatory Cells in Myeloma: Molecular Mechanisms of Dysregulation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3462-3462
Author(s):  
Rao H. Prabhala ◽  
Paola Neri ◽  
Pierfrancesco Tassone ◽  
Jooeun E. Bae ◽  
Masood A. Shammas ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Treg Cell ◽  
Cell Function ◽  
Cell Activity ◽  
T Cell Responses ◽  
Treg Cells ◽  
Cell Responses ◽  
Treg Cell Function

Abstract Multiple myeloma (MM) is characterized by production of monoclonal immunoglobulin, associated with suppressed uninvolved immunoglobulins and dysfunctional T cell responses. The biological basis of this dysfunction remains ill defined. Since T regulatory (Treg) cells play an important role in suppressing normal immune responses, we have here evaluated the potential role of Treg cells in immune dysfunction in MM. We observed a significant increase in CD4+CD25+ T cells in individuals with monoclonal gammopathy of undetermined significance (MGUS) and patients with MM compared to normal donors (25% and 26% versus 14%, respectively); however, Treg cells as measured by Foxp3 expression are significantly decreased in both MGUS (1.6±0.5%, p<0.01) and MM (1.6±0.5%, p<0.01) compared to normal donors (6.0±0.8%). Additionally, these Treg cells also do not function normally. Treg cells from patients with MM and MGUS even when added in higher proportions are unable to suppress anti-CD3-mediated T cell proliferation. This decreased number and function of Treg cells in MGUS and in MM may account, at least in part, for the non-specific increase in CD4+CD25+ T cells, thereby contributing to dysfunctional T cell responses. We have further analyzed the molecular basis for the Treg cell dysfunction in myeloma. Based on the preliminary results suggesting a role of IL-6 in Treg cell function and since both serum IL-6 and soluble IL-6 receptor levels are significantly elevated in MGUS and MM, we evaluated the role of IL-6 and its soluble receptor on Treg cell function. We observed that the addition of IL-6 and/or sIL-6 receptor to the culture leads to loss of Treg cell activity in normal donor cells similar to one observed in myeloma patients; and conversely, when Treg cells from MM patients are treated with the anti-IL-6 antibody or IL-6 receptor super antagonist, sant 7, the suppressive activity of Treg cells is restored. Additionally, we have preliminary evidence of expansion of Foxp3+ cell numbers in PBMC from MM patients following in vitro treatment with anti-IL-6 antibody. This data suggests a role of IL-6 and bone marrow microenvironment in dysfunctional Treg cells in MM and that inhibition of IL-6 signaling results in beneficial effects on T cell activity by increasing Treg cell activity. A blockade of IL-6 signaling thus emerges as a potential approach to establish immune homeostasis to improve immune function in MM.

Crucial role of physiotherapy in treating COVID-19 patients

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 967-971
Author(s):  
Poonam Thakre ◽  
Waqar M. Naqvi ◽  
Trupti Deshmukh ◽  
Nikhil Ingole ◽  
Sourabh Deshmukh
Keyword(s):  
Public Health ◽  
Distress Syndrome ◽  
Public Health Problem ◽  
Public Health Emergency ◽  
High Rate ◽  
Major Public Health Problem ◽  
Front Line ◽  
The Many ◽  
Sixth International

The emergence in China of 2019 of severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) previously provisionally names 2019-nCoV disease (COVID19) caused major global outbreak and is a major public health problem. On 30 January 2020, the WHO declared COVID19 to be the sixth international public health emergency. This present pandemic has engrossed the globe with a high rate of mortality. As a front line practitioner, physiotherapists are expected to be getting in direct contact with patients infected with the virus. That’s why it is necessary for understanding the many aspects of their role in the identification, contains, reduces and treats the symptoms of this disease. The main presentation is the involvement of respiratory system with symptoms like fever, cough, sore throat, sneezing and characteristics of pneumonia leads to ARDS(Acute respiratory distress syndrome) also land up in multiorgan dysfunction syndrome. This text describes and suggests physiotherapy management of acute COVID-19 patients. It also includes recommendations and guidelines for physiotherapy planning and management. It also covers the guidelines regarding personal care and equipment used for treatment which can be used in the treatment of acute adult patients with suspected or confirmed COVID-19.

scholarly journals Human fetal liver MSCs are more effective than adult bone marrow MSCs for their immunosuppressive, immunomodulatory, and Foxp3+ T reg induction capacity

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yi Yu ◽  
Alejandra Vargas Valderrama ◽  
Zhongchao Han ◽  
Georges Uzan ◽  
Sina Naserian ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Immune Responses ◽  
Molecular Mechanisms ◽  
Fetal Liver ◽  
Cytotoxic T Cells ◽  
Cell Contact ◽  
Adult Bone Marrow ◽  
Adult Bone

Abstract Background Mesenchymal stem cells (MSCs) exhibit active abilities to suppress or modulate deleterious immune responses by various molecular mechanisms. These cells are the subject of major translational efforts as cellular therapies for immune-related diseases and transplantations. Plenty of preclinical studies and clinical trials employing MSCs have shown promising safety and efficacy outcomes and also shed light on the modifications in the frequency and function of regulatory T cells (T regs). Nevertheless, the mechanisms underlying these observations are not well known. Direct cell contact, soluble factor production, and turning antigen-presenting cells into tolerogenic phenotypes, have been proposed to be among possible mechanisms by which MSCs produce an immunomodulatory environment for T reg expansion and activity. We and others demonstrated that adult bone marrow (BM)-MSCs suppress adaptive immune responses directly by inhibiting the proliferation of CD4+ helper and CD8+ cytotoxic T cells but also indirectly through the induction of T regs. In parallel, we demonstrated that fetal liver (FL)-MSCs demonstrates much longer-lasting immunomodulatory properties compared to BM-MSCs, by inhibiting directly the proliferation and activation of CD4+ and CD8+ T cells. Therefore, we investigated if FL-MSCs exert their strong immunosuppressive effect also indirectly through induction of T regs. Methods MSCs were obtained from FL and adult BM and characterized according to their surface antigen expression, their multilineage differentiation, and their proliferation potential. Using different in vitro combinations, we performed co-cultures of FL- or BM-MSCs and murine CD3+CD25−T cells to investigate immunosuppressive effects of MSCs on T cells and to quantify their capacity to induce functional T regs. Results We demonstrated that although both types of MSC display similar cell surface phenotypic profile and differentiation capacity, FL-MSCs have significantly higher proliferative capacity and ability to suppress both CD4+ and CD8+ murine T cell proliferation and to modulate them towards less active phenotypes than adult BM-MSCs. Moreover, their substantial suppressive effect was associated with an outstanding increase of functional CD4+CD25+Foxp3+ T regs compared to BM-MSCs. Conclusions These results highlight the immunosuppressive activity of FL-MSCs on T cells and show for the first time that one of the main immunoregulatory mechanisms of FL-MSCs passes through active and functional T reg induction.

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