craft t cell

Coordinated gene expression programs enable development and function of T cell subsets. Follicular helper T (Tfh) cells coordinate humoral immune responses by providing selective and instructive cues to germinal center B cells. Here, we show that AP-1-independent NFAT gene expression, a program associated with hyporesponsive T cell states like anergy or exhaustion, is also a distinguishing feature of Tfh cells. NFAT signaling in Tfh cells, maintained by NFAT2 autoamplification, is required for their survival...

Background: Modeling of single cell RNA-sequencing (scRNA-seq) data remains challenging due to a high percentage of zeros and data heterogeneity, so improved modeling has strong potential to benefit many downstream data analyses. The existing zero-inflated or over-dispersed models are based on aggregations at either the gene or the cell level. However, they typically lose accuracy due to a too crude aggregation at those two levels. Results: We avoid the crude approximations entailed by such aggregation through proposing an Independent Poisson Distribution (IPD) particularly at each individual entry in the scRNA-seq data matrix...

The choice to postpone treatment while awaiting genetic testing can result in significant delay in definitive therapies in patients with severe pancytopenia. Conversely, the misdiagnosis of inherited bone marrow failure (BMF) can expose patients to ineffectual and expensive therapies, toxic transplant conditioning regimens, and inappropriate use of an affected family member as a stem cell donor. To predict the likelihood of patients having acquired or inherited BMF, we developed a 2-step data-driven machine-learning model using 25 clinical and laboratory variables typically recorded at the initial clinical encounter...

Novel feed ingredients may improve poultry health, but functionality of these ingredients may vary across basal diet formulations. This study evaluated a proprietary algae ingredient's effects on broiler performance, intestinal health, systemic immunity, and metabolic/immune kinotypes between corn- or wheat-based diets. Ross 308 broilers were housed in 80 floor pens (14 birds/pen) and assigned to 1 of 4 corn or wheat-based diets ± 0.175% algae ingredient for 42 d. At the end of each 14 d starter, grower, and finisher period, 10 birds/treatment were euthanized for tissue collection to assess intestinal histomorphology, systemic immune cell populations by flow cytometry and kinotypes by peptide arrays...

Outer membrane protein A (OmpA) is one of the most abundant outer membrane proteins of Gram-negative bacteria and is known to have patterns of sequence variations at certain amino acids-allelic variation-in Escherichia coli. Here we subjected seven exemplar OmpA alleles expressed in a K-12 (MG1655) ΔompA background to further characterization. These alleles were observed to significantly impact cell surface charge (zeta potential), cell surface hydrophobicity, biofilm formation, sensitivity to killing by neutrophil elastase, and specific growth rate at 42°C and in the presence of acetate, demonstrating that OmpA is an attractive target for engineering cell surface properties and industrial phenotypes...

BACKGROUND: Microtubules (MTs) are critical for cell structure, function, and survival. MT instability may contribute to Alzheimer's disease (AD) pathogenesis as evidenced by persistent negative regulation (phosphorylation) of the neuronal microtubule-associated protein tau. Hyperphosphorylated tau, not bound to MTs, forms intraneuronal pathology that correlates with dementia and can be tracked using positron emission tomography (PET) imaging. The contribution of MT instability in AD remains unknown, though it may be more proximal to neuronal dysfunction than tau accumulation...

Pneumoconiosis is a type of occupational disease with extensive influence and serious harm. It is a systemic disease of diffuse pulmonary fibrosis caused by the inhalation of industrial dust into the lungs, and pneumoconiosis can continue to progress without further dust exposure, eventually leading to respiratory failure and death. With the wide application of new materials, new technologies and new crafting, the increasing demand for industrial materials, the survival of a large number of dust-exposed workers during the industrial boom in the 20th century, the incidence and cumulative number of pneumoconiosis cases continued to remain high, which caused a vast economic burden to the society...

The inability of CD8+ effector T cells (Teffs) to reach tumor cells is an important aspect of tumor resistance to cancer immunotherapy. The recruitment of these cells to the tumor microenvironment (TME) is regulated by integrins, a family of adhesion molecules that are expressed on T cells. Here, we show that 7HP349, a small-molecule activator of lymphocyte function-associated antigen-1 (LFA-1) and very late activation antigen-4 (VLA-4) integrin cell-adhesion receptors, facilitated the preferential localization of tumor-specific T cells to the tumor and improved antitumor response...

Preclinical studies indicate an age-associated accumulation of senescent cells across multiple organ systems. Emerging evidence suggests that tau protein accumulation, which closely correlates with cognitive decline in Alzheimer's disease and other tauopathies, drives cellular senescence in the brain. Pharmacologically clearing senescent cells in mouse models of tauopathy reduced brain pathogenesis. Compared to vehicle treated mice, intermittent senolytic administration reduced tau accumulation and neuroinflammation, preserved neuronal and synaptic density, restored aberrant cerebral blood flow, and reduced ventricular enlargement...

Tbet+ CD11c+ B cells arise during type 1 pathogen challenge, aging, and autoimmunity in mice and humans. Here, we examined the developmental requirements of this B cell subset. In acute infection, T follicular helper (Tfh) cells, but not Th1 cells, drove Tbet+ CD11c+ B cell generation through proximal delivery of help. Tbet+ CD11c+ B cells developed prior to germinal center (GC) formation, exhibiting phenotypic and transcriptional profiles distinct from GC B cells. Fate tracking revealed that most Tbet+ CD11c+ B cells developed independently of GC entry and cell-intrinsic Bcl6 expression...

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Orthohantavirus, a zoonotic virus responsible for causing human cardio-pulmonary disease, is proven to be a fatal disease. Due to the paucity of regimens to cure the disease and efficient management to eradicate this deadly virus, there is a constant need to expand in-silico approaches belonging to immunology domain to formulate best feasible peptide-based vaccine against it. In lieu of that, we have predicted and validated an epitope of nine-residue-long sequence "MIGLLSSRI". The predicted epitope has shown best interactions with HLA alleles of MHC Class II proteins, namely HLA DRB1_0101, DRB1_0401, DRB1_0405, DRB1_0701, DRB1_0901, DRB1_1302, and DRB1_1501...

CD4 T follicular helper (TFH) cells support B cells, which are critical for germinal center (GC) formation, but the importance of TFH-B cell interactions in cancer is unclear. We found enrichment of TFH cell transcriptional signature correlates with GC B cell signature and with prolonged survival in individuals with lung adenocarcinoma (LUAD). We further developed a murine LUAD model in which tumor cells express B cell- and T cell-recognized neoantigens. Interactions between tumor-specific TFH and GC B cells, as well as interleukin (IL)-21 primarily produced by TFH cells, are necessary for tumor control and effector CD8 T cell function...

Comparing competing mathematical models of complex processes is a shared goal among many branches of science. The Bayesian probabilistic framework offers a principled way to perform model comparison and extract useful metrics for guiding decisions. However, many interesting models are intractable with standard Bayesian methods, as they lack a closed-form likelihood function or the likelihood is computationally too expensive to evaluate. In this work, we propose a novel method for performing Bayesian model comparison using specialized deep learning architectures...

In traumatic brain injury (TBI), a diversity of brain resident and peripherally derived myeloid cells have the potential to worsen damage and/or to assist in healing. We define the heterogeneity of microglia and macrophage phenotypes during TBI in wild-type (WT) mice and Ccr2-/- mice, which lack macrophage influx following TBI and are resistant to brain damage. We use unbiased single-cell RNA sequencing methods to uncover 25 microglia, monocyte/macrophage, and dendritic cell subsets in acute TBI and normal brains...

BACKGROUND: Canine circovirus is a deadly pathogen of dogs and causes vasculitis and hemorrhagic enteritis. It causes lethal gastroenteritis in pigs, fox, and dogs. Canine circovirus genome contains two main (and opposite) transcription units which encode two open reading frames (ORFs), a replicase-associated protein (Rep) and the capsid (Cap) protein. The replicase protein and capsid protein consist of 303 amino acids and 270 amino acids respectively. Several immuno-informatics methods such as epitope screening, molecular docking, and molecular-dynamics simulations were used to craft peptide-based vaccine construct against canine circovirus...

Compounds in microalgae-derived feed ingredients in poultry diets may improve intestinal physiology and immunity to protect against damage induced by physiological and pathogen challenges, but mechanisms are examined sparingly. The study objective was to evaluate changes to intestinal morphology, permeability, and systemic immunity in broilers fed a proprietary microalgae ingredient during 2 separate challenge studies. In study 1, two replicate 28 d battery cage trials used 200 Ross 308 broilers each (n = 400) fed a control diet ± 0...

Multiple checkpoint mechanisms are overridden by cancer cells in order to develop into a tumor. Neoplastic cells, while constantly changing during the course of cancer progression, also craft their surroundings to meet their growing needs. This crafting involves changing cell surface receptors, affecting response to extracellular signals and secretion of signals that affect the nearby cells and extracellular matrix architecture. This chapter briefly comprehends the non-cancer cells facilitating the cancer growth and elaborates on the notable role of the CCR9-CCL25 chemokine axis in shaping the tumor microenvironment (TME), directly and via immune cells...

T follicular helper (Tfh) cells cognately guide differentiation of antigen-primed B cells in secondary lymphoid tissues. 'Tfh-like' populations not expressing the canonical Tfh cell transcription factor BCL6 have also been described, which can aid particular aspects of B cell differentiation. Tfh and Tfh-like cells are essential for protective and pathological humoral immunity. These CD4+ T cells that help B cells are polarized to produce diverse combinations of cytokines and chemokine receptors and can be grouped into distinct subsets that promote antibodies of different isotype, affinity, and duration, according to the nature of immune challenge...

T follicular regulatory cells, or Tfr cells, are a discernable population of regulatory T (Treg) cells that migrate to the B cell follicle and germinal center (GC) upon immune challenge. These cells express the transcription factor Bcl6, the master regulator required for development and differentiation of T follicular helper cells, and are among a group of previously described Treg cells that use T helper cell-associated transcription factors to adapt their regulatory function to diverse milieus for maintenance of immune homeostasis...