Control of CD4 T cells to restrain inflammatory diseases via eukaryotic elongation factor 2 kinase.

CD4 T cells, particularly IL-17-secreting helper CD4 T cells, play a central role in the inflammatory processes underlying autoimmune disorders. Eukaryotic Elongation Factor 2 Kinase (eEF2K) is pivotal in CD8 T cells and has important implications in vascular dysfunction and inflammation-related diseases such as hypertension. However, its specific immunological role in CD4 T cell activities and related inflammatory diseases remains elusive.

NAC1 confines virus-specific memory formation of CD4 T cells through the ROCK1-mediated pathway.

Nucleus accumbens-associated protein 1 (NAC1), a transcriptional cofactor, has been found to play important roles in regulating regulatory T cells, CD8 T cells, and antitumor immunity, but little is known about its effects on T-cell memory. In this study, we found that NAC1 expression restricts memory formation of CD4 T cells during viral infection. Analysis of CD4 T cells from wild-type (WT) and NAC1-deficient ( ) mice showed that NAC1 is essential for T-cell metabolism, including glycolysis and oxidative phosphorylation, and supports CD4 T-cell survival in vitro.

Engineering live attenuated vaccines: Old dogs learning new tricks.

Autoimmune diseases such as rheumatoid arthritis and type 1 diabetes are increasingly common global problems. Concerns about increases in the prevalence of such diseases and the limited efficacy of conventional treatment regimens necessitates new therapies to address these challenges. Autoimmune disease severity and dysbiosis are interconnected.

T Cell Response to SARS-CoV-2 Coinfection and Comorbidities.

For the past three years, COVID-19 has become an increasing global health issue. Adaptive immune cells, especially T cells, have been extensively investigated in regard to SARS-CoV-2 infection. However, human health and T cell responses are also impacted by many other pathogens and chronic diseases.

A metabolically engineered bacterium controls autoimmunity and inflammation by remodeling the pro-inflammatory microenvironment.

Immunotherapy has led to impressive advances in the treatment of autoimmune and pro-inflammatory disorders; yet, its clinical outcomes remain limited by a variety of factors including the pro-inflammatory microenvironment (IME). Discovering effective immunomodulatory agents, and the mechanisms by which they control disease, will lead to innovative strategies for enhancing the effectiveness of current immunotherapeutic approaches. We have metabolically engineered an attenuated bacterial strain (i.

Expression of NAC1 Restrains the Memory Formation of CD8 T Cells during Viral Infection.

Nucleus accumbens-associated protein 1 (NAC1) is a transcription co-factor that has been shown to possess multiple roles in stem cell and cancer biology. However, little is known about its roles in regulation of the immune system. In the current study, we observed that expression of NAC1 impacted the survival of CD8 T cells in vitro.

NAC1 modulates autoimmunity by suppressing regulatory T cell-mediated tolerance.

We report here that nucleus accumbens-associated protein-1 (NAC1), a nuclear factor of the Broad-complex, Tramtrack, Bric-a-brac/poxvirus and zinc finger (BTB/POZ) gene family, is a negative regulator of FoxP3 in regulatory T cells (T) and a critical determinant of immune tolerance. Phenotypically, NAC1 mice showed substantial tolerance to the induction of autoimmunity and generated a larger amount of CD4 T that exhibit a higher metabolic profile and immune-suppressive activity, increased acetylation and expression of FoxP3, and slower turnover of this transcription factor. Treatment of T with the proinflammatory cytokines interleukin-1β or tumor necrosis factor-α induced a robust up-regulation of NAC1 but evident down-regulation of FoxP3 as well as the acetylated FoxP3.

Elongation factor-2 kinase is a critical determinant of the fate and antitumor immunity of CD8 T cells.

eEF-2K has important roles in stress responses and cellular metabolism. We report here a previously unappreciated but critical role of eEF-2K in regulating the fate and cytocidal activity of CD8 T cells. CD8 T cells from eEF-2K KO mice were more proliferative but had lower survival than their wild-type counterparts after their activation, followed by occurrence of premature senescence and exhaustion.

Insights Into the Pathologic Roles and Regulation of Eukaryotic Elongation Factor-2 Kinase.

Eukaryotic Elongation Factor-2 Kinase (eEF2K) acts as a negative regulator of protein synthesis, translation, and cell growth. As a structurally unique member of the alpha-kinase family, eEF2K is essential to cell survival under stressful conditions, as it contributes to both cell viability and proliferation. Known as the modulator of the global rate of protein translation, eEF2K inhibits eEF2 (eukaryotic Elongation Factor 2) and decreases translation elongation when active.

Stem Cell-Derived Viral Antigen-Specific T Cells Suppress HIV Replication and PD-1 Expression on CD4+ T Cells.

The viral antigen (Ag)-specific CD8+ cytotoxic T lymphocytes (CTLs) derived from pluripotent stem cells (PSCs), i.e., PSC-CTLs, have the ability to suppress the human immunodeficiency virus (HIV) infection.

Metabolic Reprogramming and Reactive Oxygen Species in T Cell Immunity.

T cells undergo metabolic reprogramming and multiple biological processes to satisfy their energetic and biosynthetic demands throughout their lifespan. Several of these metabolic pathways result in the generation of reactive oxygen species (ROS). The imbalance between ROS generation and scavenging could result in severe damage to the cells and potential cell death, ultimately leading to T cell-related diseases.

An optimized protocol for the generation of HBV viral antigen-specific T lymphocytes from pluripotent stem cells.

In T cell-based cancer immunotherapy, tumor antigen (Ag)-specific CD8 cytotoxic T lymphocytes (CTLs) can specifically target tumor Ags on malignant cells. This promising approach drove us to adopt this strategy of T cell transfer (ACT)-based immunotherapy for chronic viral infections. Here, we describe the generation of hepatitis B virus (HBV) Ag-specific CTLs from induced pluripotent stem cells (iPSCs), i.

Development of CAR-T Cell Persistence in Adoptive Immunotherapy of Solid Tumors.

Chimeric antigen receptor (CAR) T (CAR-T) cell transfer has made great success in hematological malignancies, but only shown a limited effect on solid tumors. One of the major hurdles is the poor persistence of infused cells derived from activation/expansion and repeated antigen encounter after re-infusion. Bcl-xL has been demonstrated to play an important role on normal T cell survival and function as well as genetically engineered cells.

Autophagy in T-cell differentiation, survival and memory.

Over the past decade, autophagy has emerged as a critical regulatory mechanism of the immune system through critically controlling various aspects of T cell biology and determining the fate of different T cell subsets. Autophagy maintains T cell development and survival by regulating the degradation of organelles and apoptotic proteins. The autophagic process also impacts the formation of memory T cells.

Stem Cell-Derived Viral Antigen-Specific T Cells Suppress HBV Replication through Production of IFN-γ and TNF-⍺.

The viral antigen (Ag)-specific CD8 cytotoxic T lymphocytes (CTLs) derived from pluripotent stem cells (PSCs), i.e., PSC-CTLs, have the ability to suppress hepatitis B virus (HBV) infection.

Heat Shock Proteins in Cancer Immunotherapy.

Heat shock proteins (HSPs) are highly conserved molecular chaperones with divergent roles in various cellular processes. The HSPs are classified according to their molecular size as HSP27, HSP40, HSP60, HSP70, and HSP90. The HSPs prevent nonspecific cellular aggregation of proteins by maintaining their native folding energetics.

Targeting Stem Cell-Derived Tissue-Associated Regulatory T Cells for Type 1 Diabetes Immunotherapy.

Purpose Of Review: Type 1 diabetes (T1D) is an autoimmune disease in which the immune cells selectively destroy the pancreatic beta (β) cells and results in the deficiency of insulin production. The optimal treatment strategy for T1D should be preventing of β-cell destruction in the pancreas. The purpose of this review is to discuss the immunological therapeutic mechanisms that will help to understand the development and control of β-cell destruction.

Stem cell-derived tissue-associated regulatory T cells suppress the activity of pathogenic cells in autoimmune diabetes.

The autoantigen-specific Tregs from pluripotent stem cells (PSCs), i.e., PSC-Tregs, have the ability to suppress autoimmunity.

Janus kinase 3 regulates adherens junctions and epithelial mesenchymal transition through β-catenin.

Compromise in adherens junctions (AJs) is associated with several chronic inflammatory diseases. We reported previously that Janus kinase 3, a non-receptor tyrosine kinase, plays a crucial role in AJ formation through its interaction with β-catenin. In this report, we characterize the structural determinants responsible for Jak3 interactions with β-catenin and determine the functional implications of previously unknown tyrosine residues on β-catenin phosphorylated by Jak3.

Natural mineral-rich water ingestion by ovariectomized fructose-fed Sprague-Dawley rats: effects on sirtuin 1 and glucocorticoid signaling pathways.

Objective: Prevention or induction of metabolic disorders and obesity depend on estrogen signaling and/or exogenous factors, such as mineral content in diet. The protective effects of a Portuguese natural mineral-rich water against the induction of metabolic syndrome in fructose-fed male Sprague-Dawley rats have been reported. The present study was designed to assess the impact of this mineral-rich water on fructose-fed estrogen-deficient female Sprague-Dawley rats.

Altered virulence potential of Salmonella Enteritidis cultured in different foods: A cumulative effect of differential gene expression and immunomodulation.

Salmonella enterica serovars Enteritidis (S. Enteritidis) is one of the most common causes of food borne illness. Bacterial growth environment plays an important role in regulating gene expression thereby affecting the virulence profile of the bacteria.

Lactobacillus acidophilus binds to MUC3 component of cultured intestinal epithelial cells with highest affinity.

Lactobacillus strains have been shown to adhere to the mucosal components of intestinal epithelial cells. However, established in vitro adhesion assays have several drawbacks in assessing the adhesion of new Lactobacillus strains. The present study aimed to compare the adhesion of four different Lactobacillus strains and select the most adherent microbe, based on in silico approach supported by in vitro results.

Molecular modeling, simulation and virtual screening of MurD ligase protein from Salmonella typhimurium LT2.

The Mur enzymes of the peptidoglycan biosynthesis pathway constitute ideal targets for the design of new classes of antimicrobial inhibitors in Gram-negative bacteria. We built a homology model of MurD of Salmonella typhimurium LT2 using MODELLER (9v12) software. 'The homology model was subjected to energy minimization by molecular dynamics (MD) simulation study with GROMACS software for a simulation time of 20 ns in water environment.

Mercaptoundecanoic acid capped palladium nanoparticles in a SAPO 34 membrane: a solution for enhancement of H₂/CO₂ separation efficiency.

In this work, the high quality Pd/SAPO 34 membranes were grown on the support using a secondary (seeded) growth hydrothermal technique followed by insertion of 11-mercaptoundecanoic acid capped palladium (MUA-Pd) nanoparticles (NPs) to the membrane surface. For this, first, the indigenous low cost clay-alumina support was treated with poly diallyldimethylammonium chloride (PolyDADMAC) polymer, and subsequently, a seed layer of SAPO 34 crystals was deposited homogeneously in a regular orientation. Since PolyDADMAC is a high charge density cationic polymer, it assisted in reversing the charge of the support surface and produced an attractive electrostatic interaction between the support and zeolite crystals.

In vitro evaluation of anti-infective activity of a Lactobacillus plantarum strain against Salmonella enterica serovar Enteritidis.

Background: Salmonella enterica serovar Enteritidis infections are known to exhibit worldwide prevalence with increased morbidity and mortality. The conventional strategies like antibiotic therapy and vaccination have not only proved to be of sub-optimal efficacy but also led to the development of multidrug resistant strains of Salmonella. Antimicrobial activities of probiotics against various enteropathogens and other health promoting effects have assumed greater significance in recent years.