scholarly journals Epigenetic Modifications in T Cells

Hypertension ◽  
2020 ◽  
Vol 75 (2) ◽  
pp. 372-382 ◽  
Author(s):  
John Henry Dasinger ◽  
Ammar J. Alsheikh ◽  
Justine M. Abais-Battad ◽  
Xiaoqing Pan ◽  
Daniel J. Fehrenbach ◽  
...  
Keyword(s):  
Dna Methylation ◽  
T Cells ◽  
Immune System ◽  
Renal Damage ◽  
Cell Function ◽  
Immune Cell ◽  
Dna Methyltransferases ◽  
Epigenetic Modifications ◽  
High Salt ◽  
Immune System Activation

The SS (Dahl salt sensitive) rat is an established model of hypertension and renal damage that is accompanied with immune system activation in response to a high-salt diet. Investigations into the effects of sodium-independent and dependent components of the diet were shown to affect the disease phenotype with SS/MCW (JrHsdMcwi) rats maintained on a purified diet (AIN-76A) presenting with a more severe phenotype relative to grain-fed SS/CRL (JrHsdMcwiCrl) rats. Since contributions of the immune system, environment, and diet are documented to alter this phenotype, this present study examined the epigenetic profile of T cells isolated from the periphery and the kidney from these colonies. T cells isolated from kidneys of the 2 colonies revealed that transcriptomic and functional differences may contribute to the susceptibility of hypertension and renal damage. In response to high-salt challenge, the methylome of T cells isolated from the kidney of SS/MCW exhibit a significant increase in differentially methylated regions with a preference for hypermethylation compared with the SS/CRL kidney T cells. Circulating T cells exhibited similar methylation profiles between colonies. Utilizing transcriptomic data from T cells isolated from the same animals upon which the DNA methylation analysis was performed, a predominant negative correlation was observed between gene expression and DNA methylation in all groups. Lastly, inhibition of DNA methyltransferases blunted salt-induced hypertension and renal damage in the SS/MCW rats providing a functional role for methylation. This study demonstrated the influence of epigenetic modifications to immune cell function, highlighting the need for further investigations.

scholarly journals Nanoengineering of Immune Cell Function

2009 ◽  
Vol 1209 ◽  
Author(s):  
Keyue Shen ◽  
Michael C Milone ◽  
Michael L. Dustin ◽  
Lance Cameron Kam
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cell Function ◽  
Immune Cell ◽  
Cell Communication ◽  
Cell Therapies ◽  
Nano Scale

AbstractT lymphocytes are a key regulatory component of the adaptive immune system. Understanding how the micro- and nano-scale details of the extracellular environment influence T cell activation may have wide impact on the use of T cells for therapeutic purposes. In this article, we examine how the micro- and nano-scale presentation of ligands to cell surface receptors, including microscale organization and nanoscale mobility, influences the activation of T cells. We extend these studies to include the role of cell-generated forces, and the rigidity of the microenvironment, on T cell activation. These approaches enable delivery of defined signals to T cells, a step toward understanding the cell-cell communication in the immune system, and developing micro/nano- and material- engineered systems for tailoring immune responses for adoptive T cell therapies.

scholarly journals Human Tissue-Resident Memory T Cells in the Maternal–Fetal Interface. Lost Soldiers or Special Forces?

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2699
Author(s):  
Caitlin S. DeJong ◽  
Nicholas J. Maurice ◽  
Stephen A. McCartney ◽  
Martin Prlic
Keyword(s):  
T Cells ◽  
Immune System ◽  
Cell Function ◽  
Immune Cell ◽  
Memory T Cells ◽  
Critical Role ◽  
Immune Cell Function ◽  
Histocompatibility Complex ◽  
Resident Memory T Cells ◽  
Maternal Fetal Interface

The immune system plays a critical role during pregnancy, but the specific mechanisms and immune cell function needed to support pregnancy remain incompletely understood. Despite decades of research efforts, it is still unclear how the immune system maintains tolerance of fetal-derived tissues, which include most cells of the placenta and of course the fetus itself, without forfeiting the ability to protect against harmful infections. T cells recognize antigen in the context of major histocompatibility complex (MHC) encoded proteins, but classical MHC class I and II expression are diminished in fetal-derived cells. Can T cells present at the maternal–fetal interface (MFI) protect these cells from infection? Here we review what is known in regard to tissue-resident memory T (Trm) cells at the MFI. We mainly focus on how Trm cells can contribute to protection in the context of the unique features of the MFI, such as limited MHC expression as well as the temporary nature of the MFI, that are not found in other tissues.

Abstract 562: Plgf is Crucial for the Hypertensive Response and T Cells Infiltration in Target Organs Induced by Angii

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Daniela Carnevale ◽  
Fabio Pallante ◽  
Valentina Fardella ◽  
Massimiliano De Lucia ◽  
Stefania Fardella ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Organ Damage ◽  
Central Moment ◽  
Immune System Activation ◽  
Target Organs ◽  
Main Components

Although several therapeutic strategies have been developed against the main components involved in blood pressure (BP) regulation, an optimum control in some hypertensive patients is still flawed, suggesting that mechanisms so far unidentified, sustain BP increase. Interestingly, an emerging area of investigation revealed that adaptive immunity is central in hypertension, since mice devoid of lymphocytes are protected from hypertension, and adoptive transfer of T cells, but not B cells, restores the typical hypertensive response. How hypertensive stimuli can afford this, still represents a fascinating enigma, challenging the search for molecular players, capable to bridge vascular responses to immunity and probably orchestrating the still unveiled role of immune system in hypertension. Among the manifold cytokines and inflammatory mediators, Placental Growth Factor (PlGF), belonging to a family of VEGF related angiogenic factors, caught our attention, given its role of “angiogenic cytokine” and its expression by cells of both the cardiovascular and the immune system. Moreover, it has also been recently shown that PlGF is secreted in vascular cells in response to AngII. Thus, we hypothesized that PlGF might recruit a selected type of immune cell, expressing its receptor VEGFR1, influencing the process of T cells activation during hypertensive challenges. We found that the typical hypertensive response induced by chronic AngII infusion, was completely prevented in mice with genetic deletion of PlGF, as well as the typical end organ damage induced by hypertension, i.e. cardiac hypertrophy, renal damage, microvascular rarefaction and immune cells infiltration in target organs. To determine whether the involvement of PlGF in immune system activation and T cells infiltration during AngII-induced hypertension had a causal role or was merely a consequence of the failure in BP raise, we analyzed both vessels and kidneys, early after AngII infusion, i.e. before BP increase. Strikingly, PlGF absence protected from early infiltration of both CD4+ and CD8+ T cells. Overall our data indicate that PlGF is a pivotal player in the molecular mechanisms activating immune system recruitment during an hypertensive challenge, a central moment in the increase in BP.

scholarly journals Recovery of the immune system after exercise

2017 ◽  
Vol 122 (5) ◽  
pp. 1077-1087 ◽  
Author(s):  
Jonathan M. Peake ◽  
Oliver Neubauer ◽  
Neil P. Walsh ◽  
Richard J. Simpson
Keyword(s):  
T Cells ◽  
Immune System ◽  
Cell Function ◽  
Immune Cell ◽  
Physiological Stress ◽  
Current Knowledge ◽  
Ex Vivo ◽  
Γδ T Cells ◽  
Peripheral Tissues ◽  
Recovery Sleep

The notion that prolonged, intense exercise causes an “open window” of immunodepression during recovery after exercise is well accepted. Repeated exercise bouts or intensified training without sufficient recovery may increase the risk of illness. However, except for salivary IgA, clear and consistent markers of this immunodepression remain elusive. Exercise increases circulating neutrophil and monocyte counts and reduces circulating lymphocyte count during recovery. This lymphopenia results from preferential egress of lymphocyte subtypes with potent effector functions [e.g., natural killer (NK) cells, γδ T cells, and CD8+ T cells]. These lymphocytes most likely translocate to peripheral sites of potential antigen encounter (e.g., lungs and gut). This redeployment of effector lymphocytes is an integral part of the physiological stress response to exercise. Current knowledge about changes in immune function during recovery from exercise is derived from assessment at the cell population level of isolated cells ex vivo or in blood. This assessment can be biased by large changes in the distribution of immune cells between blood and peripheral tissues during and after exercise. Some evidence suggests that reduced immune cell function in vitro may coincide with changes in vivo and rates of illness after exercise, but more work is required to substantiate this notion. Among the various nutritional strategies and physical therapies that athletes use to recover from exercise, carbohydrate supplementation is the most effective for minimizing immune disturbances during exercise recovery. Sleep is an important aspect of recovery, but more research is needed to determine how sleep disruption influences the immune system of athletes.

scholarly journals Interleukins and Interleukin Receptors Evolutionary History and Origin in Relation to CD4+ T Cell Evolution

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 813
Author(s):  
Norwin Kubick ◽  
Pavel Klimovich ◽  
Patrick Henckell Flournoy ◽  
Irmina Bieńkowska ◽  
Marzena Łazarczyk ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Positive Selection ◽  
Cd4 T Cells ◽  
Cell Function ◽  
Single Gene ◽  
Ancestral Reconstruction ◽  
Critical Function ◽  
Interleukin Receptors

Understanding the evolution of interleukins and interleukin receptors is essential to control the function of CD4+ T cells in various pathologies. Numerous aspects of CD4+ T cells’ presence are controlled by interleukins including differentiation, proliferation, and plasticity. CD4+ T cells have emerged during the divergence of jawed vertebrates. However, little is known about the evolution of interleukins and their origin. We traced the evolution of interleukins and their receptors from Placozoa to primates. We performed phylogenetic analysis, ancestral reconstruction, HH search, and positive selection analysis. Our results indicated that various interleukins' emergence predated CD4+ T cells divergence. IL14 was the most ancient interleukin with homologs in fungi. Invertebrates also expressed various interleukins such as IL41 and IL16. Several interleukin receptors also appeared before CD4+ T cells divergence. Interestingly IL17RA and IL17RD, which are known to play a fundamental role in Th17 CD4+ T cells first appeared in mollusks. Furthermore, our investigations showed that there is not any single gene family that could be the parent group of interleukins. We postulate that several groups have diverged from older existing cytokines such as IL4 from TGFβ, IL10 from IFN, and IL28 from BCAM. Interleukin receptors were less divergent than interleukins. We found that IL1R, IL7R might have diverged from a common invertebrate protein that contained TIR domains, conversely, IL2R, IL4R and IL6R might have emerged from a common invertebrate ancestor that possessed a fibronectin domain. IL8R seems to be a GPCR that belongs to the rhodopsin-like family and it has diverged from the Somatostatin group. Interestingly, several interleukins that are known to perform a critical function for CD4+ T cells such as IL6, IL17, and IL1B have gained new functions and evolved under positive selection. Overall evolution of interleukin receptors was not under significant positive selection. Interestingly, eight interleukin families appeared in lampreys, however, only two of them (IL17B, IL17E) evolved under positive selection. This observation indicates that although lampreys have a unique adaptive immune system that lacks CD4+ T cells, they could be utilizing interleukins in homologous mode to that of the vertebrates' immune system. Overall our study highlights the evolutionary heterogeneity within the interleukins and their receptor superfamilies and thus does not support the theory that interleukins evolved solely in jawed vertebrates to support T cell function. Conversely, some of the members are likely to play conserved functions in the innate immune system.

scholarly journals Cellular and metabolic mechanisms of nutrient actions in immune function

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Philip Newsholme
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Vitamin D ◽  
Immune System ◽  
Cell Function ◽  
Immune Cell ◽  
Cell Structure ◽  
Nutritional Intervention ◽  
Immune Cell Function ◽  
And Function

AbstractVarious nutrients can change cell structure, cellular metabolism, and cell function which is particularly important for cells of the immune system as nutrient availability is associated with the activation and function of diverse immune subsets. The most important nutrients for immune cell function and fate appear to be glucose, amino acids, fatty acids, and vitamin D. This perspective will describe recently published information describing the mechanism of action of prominent nutritional intervention agents where evidence exists as to their action and potency.

Abstract P332: Role of T-Lymphocytes in the Long-Term Blood Pressure and Renal Disease Effects of Acute Renal Ischemia-Reperfusion Injury

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Bernardo Lopez ◽  
Galina Petrova ◽  
Justine M Abais-Battad ◽  
Hayley Lund ◽  
Daniel Fehrenbach ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Renal Damage ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Immunosuppressive Agents ◽  
High Salt ◽  
Renal Ischemia ◽  
Salt Sensitive Hypertension

Epidemiological data indicates that acute kidney injury (AKI) is an independent risk factor for the development of hypertension and chronic kidney disease in patients. Previous studies demonstrated that rats develop sodium-dependent hypertension and kidney damage following experimental AKI induced by a renal ischemia-reperfusion (IR) insult; furthermore, these high salt deleterious effects could be blunted by administration of immunosuppressive agents. The present study was performed on Dahl SS (SS) rats and SS rats with a null mutation in the CD247 gene (SS-CD247) leading to depletion of T-lymphocytes in order to specifically examine the role of T cells in this response (n=5-6 rats/group). As assessed by serum creatinine (SCr) levels, no difference was observed in the initial response to IR injury between SS and SS-CD247: SCr increased from 0.44±0.03 to 2.16±0.32 mg/dl in SS rats 24 hours after an initial 30 minute period of renal ischemia and returned to control levels after 8 days of recovery. Moreover, no differences were noted in mean arterial pressure (MAP) or albumin excretion rate (UAlb) between SS and SS-CD247 after 43 days of recovery from IR injury while the rats were maintained on a low salt (0.4% NaCl) diet. When the rats were fed a 4.0% NaCl diet for two weeks, MAP and UAlb significantly increased in the sham SS to 178±9 mmHg and 189±25 mg/day, respectively; values significantly greater than observed in the sham SS-CD247 rats (148±2 mmHg and 87±17 mg/day). As expected, the SS rats recovered from IR injury demonstrated an exaggerated increase in MAP (peaking at 183±2 mmHg) and UAlb (275±54 mg/day) in response to high salt. There was no difference in the number of total CD3+ lymphocytes in the kidneys of IR and sham SS after high salt, though the ratio of CD4+/CD8+ T cells was increased in the IR group. Compared to sham CD247, an exaggerated elevation of MAP (157±9 mmHg) and UAlb (210±32 mg/day) was also observed in the SS-CD247 rats recovered from IR injury, demonstrating enhanced responsiveness following IR injury in animals lacking T cells. These data indicate that T lymphocytes amplify salt-sensitive hypertension and renal damage, but other mechanisms also mediate the salt-sensitive hypertension and renal damage that occurs in animals recovered from IR injury.

scholarly journals The Roles of Human DNA Methyltransferases and Their Isoforms in Shaping the Epigenome

Genes ◽  
2019 ◽  
Vol 10 (2) ◽  
pp. 172 ◽  
Author(s):  
Hemant Gujar ◽  
Daniel Weisenberger ◽  
Gangning Liang
Keyword(s):  
Dna Methylation ◽  
Cytosine Methylation ◽  
De Novo ◽  
Ring Finger ◽  
Dna Methyltransferases ◽  
Epigenetic Modifications ◽  
Hard Copy ◽  
Physiological Processes ◽  
New Gene ◽  
Cpg Dinucleotide

A DNA sequence is the hard copy of the human genome and it is a driving force in determining the physiological processes in an organism. Concurrently, the chemical modification of the genome and its related histone proteins is dynamically involved in regulating physiological processes and diseases, which overall constitutes the epigenome network. Among the various forms of epigenetic modifications, DNA methylation at the C-5 position of cytosine in the cytosine–guanine (CpG) dinucleotide is one of the most well studied epigenetic modifications. DNA methyltransferases (DNMTs) are a family of enzymes involved in generating and maintaining CpG methylation across the genome. In mammalian systems, DNA methylation is performed by DNMT1 and DNMT3s (DNMT3A and 3B). DNMT1 is predominantly involved in the maintenance of DNA methylation during cell division, while DNMT3s are involved in establishing de novo cytosine methylation and maintenance in both embryonic and somatic cells. In general, all DNMTs require accessory proteins, such as ubiquitin-like containing plant homeodomain (PHD) and really interesting new gene (RING) finger domain 1 (UHRF1) or DNMT3-like (DNMT3L), for their biological function. This review mainly focuses on the role of DNMT3B and its isoforms in de novo methylation and maintenance of DNA methylation, especially with respect to their role as an accessory protein.

scholarly journals Prolonged activation of nasal immune cell populations and development of tissue-resident SARS-CoV-2 specific CD8 T cell responses following COVID-19

2021 ◽  
Author(s):  
Anna H.E. Roukens ◽  
Marion König ◽  
Tim Dalebout ◽  
Tamar Tak ◽  
Shohreh Azimi ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Nasal Mucosa ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Upper Airway ◽  
Effector Memory ◽  
Long Term Effects ◽  
Activated T Cells

AbstractThe immune system plays a major role in Coronavirus Disease 2019 (COVID-19) pathogenesis, viral clearance and protection against re-infection. Immune cell dynamics during COVID-19 have been extensively documented in peripheral blood, but remain elusive in the respiratory tract. We performed minimally-invasive nasal curettage and mass cytometry to characterize nasal immune cells of COVID-19 patients during and 5-6 weeks after hospitalization. Contrary to observations in blood, no general T cell depletion at the nasal mucosa could be detected. Instead, we observed increased numbers of nasal granulocytes, monocytes, CD11c+ NK cells and exhausted CD4+ T effector memory cells during acute COVID-19 compared to age-matched healthy controls. These pro-inflammatory responses were found associated with viral load, while neutrophils also negatively correlated with oxygen saturation levels. Cell numbers mostly normalized following convalescence, except for persisting CD127+ granulocytes and activated T cells, including CD38+ CD8+ tissue-resident memory T cells. Moreover, we identified SARS-CoV-2 specific CD8+ T cells in the nasal mucosa in convalescent patients. Thus, COVID-19 has both transient and long-term effects on the immune system in the upper airway.

scholarly journals Activation of Bone Marrow Adaptive Immunity in Type 2 Diabetes: Rescue by Co-stimulation Modulator Abatacept

2021 ◽  
Vol 12 ◽  
Author(s):  
Marianna Santopaolo ◽  
Niall Sullivan ◽  
Anita Coral Thomas ◽  
Valeria Vincenza Alvino ◽  
Lindsay B. Nicholson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bone Marrow ◽  
T Cells ◽  
Insulin Sensitivity ◽  
Adaptive Immunity ◽  
Cell Function ◽  
Immune Cell ◽  
Low Grade ◽  
Cardiac Damage

Background: Chronic low-grade inflammation and alterations in innate and adaptive immunity were reported in Type 2 diabetes (T2D). Here, we investigated the abundance and activation of T cells in the bone marrow (BM) of patients with T2D. We then verified the human data in a murine model and tested if the activation of T cells can be rescued by treating mice with abatacept, an immunomodulatory drug employed for the treatment of rheumatoid arthritis. Clinical evidence indicated abatacept can slow the decline in beta-cell function.Methods: A cohort of 24 patients (12 with T2D) undergoing hip replacement surgery was enrolled in the study. Flow cytometry and cytokine analyses were performed on BM leftovers from surgery. We next compared the immune profile of db/db and control wt/db mice. In an additional study, db/db mice were randomized to receive abatacept or vehicle for 4 weeks, with endpoints being immune cell profile, indices of insulin sensitivity, and heart performance.Results: Patients with T2D showed increased frequencies of BM CD4+ (2.8-fold, p = 0.001) and CD8+ T cells (1.8-fold, p = 0.01), with the upregulation of the activation marker CD69 and the homing receptor CCR7 in CD4+ (1.64-fold, p = 0.003 and 2.27-fold, p = 0.01, respectively) and CD8+ fractions (1.79-fold, p = 0.05 and 1.69-fold, p = 0.02, respectively). These differences were confirmed in a multivariable regression model. CCL19 (CCR7 receptor ligand) and CXCL10/11 (CXCR3 receptor ligands), implicated in T-cell migration and activation, were the most differentially modulated chemokines. Studies in mice confirmed the activation of adaptive immunity in T2D. Abatacept reduced the activation of T cells and the levels of proinflammatory cytokines and improved cardiac function but not insulin sensitivity.Conclusions: Results provide proof-of-concept evidence for the activation of BM adaptive immunity in T2D. In mice, treatment with abatacept dampens the activation of adaptive immunity and protects from cardiac damage.

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