scholarly journals Neutrophils Suppress Mucosal-Associated Invariant T Cells

2019 ◽  
Author(s):  
M Schneider ◽  
RF Hannaway ◽  
R Lamichhane ◽  
SM de la Harpe ◽  
JDA Tyndall ◽  
...  
Keyword(s):  
Fungal Pathogens ◽  
Cell Activation ◽  
Cell Types ◽  
Feedback Mechanism ◽  
Cell Contact ◽  
Mait Cells ◽  
Mucosal Tissues ◽  
A Cell ◽  
Neutrophil Survival ◽  
Pathogen Clearance

AbstractMucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes that are abundant in mucosal tissues and the liver where they can respond rapidly to a broad range of riboflavin producing bacterial and fungal pathogens. Neutrophils, which are recruited early to sites of infection, play a non-redundant role in pathogen clearance and are crucial for controlling infection. The interaction of these two cell types is poorly studied. Here, we investigated both the effect of neutrophils on MAIT cell activation and the effect of activated MAIT cells on neutrophils. We show that neutrophils suppress the activation of MAIT cells by a cell-contact and H2O2dependent mechanism. Moreover, highly activated MAIT cells were able to produce high levels of TNFα that induced neutrophil death. We therefore provide evidence for a negative regulatory feedback mechanism in which neutrophils prevent over-activation of MAIT cells and, in turn, MAIT cells limit neutrophil survival.

scholarly journals MR1-Restricted T Cells in Cancer Immunotherapy

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2145
Author(s):  
Pedro Flores-Villanueva ◽  
Navid Sobhani ◽  
Xu Wang ◽  
Yong Li
Keyword(s):  
T Cells ◽  
Cytotoxic T Cells ◽  
Acid Synthesis ◽  
Cell Receptor ◽  
Dependent Manner ◽  
Mait Cells ◽  
Mucosal Tissues ◽  
Wide Range ◽  
A Cell ◽  
Cell Membrane Protein

Major histocompatibility complex class I-related (MR1) was first identified as a cell membrane protein involved in the development and expansion of a unique set of T cells expressing an invariant T-cell receptor (TCR) α-chain. These cells were initially discovered in mucosal tissues, such as the intestinal mucosa, so they are called mucosal-associated invariant T (MAIT) cells. MR1 senses the presence of intermediate metabolites of riboflavin and folic acid synthesis that have been chemically modified by the side-products of glycolysis, glyoxal or methylglyoxal. These modified metabolites form complexes with MR1 and translocate from the endoplasmic reticulum to the plasma membrane where MAIT cells’ TCRs recognize them. Recent publications report that atypical MR1-restricted cytotoxic T cells, differing from MAIT cells in TCR usage, antigen, and transcription factor profile, recognize an as yet unknown cancer-specific metabolite presented by MR1 in cancer cells. This metabolite may represent another class of neoantigens, beyond the neo-peptides arising from altered tumor proteins. In an MR1-dependent manner, these MR1-restricted T cells, while sparing noncancerous cells, kill many cancer cell lines and attenuate cell-line-derived and patient-derived xenograft tumors. As MR1 is monomorphic and expressed in a wide range of cancer tissues, these findings raise the possibility of universal pan-cancer immunotherapies that are dependent on cancer metabolites.

scholarly journals Modeling the relevance of immune and metabolic cues in the macrophage/fibroblast interplay during fibrosis

2021 ◽  
Author(s):  
Elisa Setten ◽  
Alessandra Castagna ◽  
Josue Nava-Sedeno ◽  
Jonathan Weber ◽  
Roberta Carriero ◽  
...  
Keyword(s):  
Interstitial Fibrosis ◽  
Cell Types ◽  
Cell Contact ◽  
Tubular Atrophy ◽  
Immune Phenotyping ◽  
A Cell ◽  
Inflammatory Infiltrates ◽  
Favorable Conditions ◽  
The Impact

Abstract Fibrosis is a progressive biological process leading to organ dysfunction in different clinical settings. As fibroblasts and macrophages are known as key cellular players for fibrosis development, we adopted an in vitro model to define the functional effects of inflammation, hypoxia, and the adaptive immune context on their functional interplay with respect to fibrosis development. Transcriptomic analysis defined the impact of each parameter, acting alone or in combination, on functional properties of both cell types, exposed individually or in a cell-cell contact. These in vitro signatures were matched with transcriptomic profiles generated on laser-captured glomeruli and cortical tubulointerstitial area isolated from human transplanted kidneys with advanced stages of glomerulosclerosis and interstitial fibrosis/tubular atrophy, two clinically relevant conditions associated with organ failure in renal allografts. In vitro signatures were also used to instruct the development of a mathematical model predicting the relevance of each parameter in fibrosis development scenario, which indicated tolerance to inflammatory infiltrates under otherwise favorable conditions and defined an operative window in which hypoxia exerts a crucial role, supported by the degree of inflammation. Observed signatures and model-based predictions strongly suggested that irreversible fibrosis development is the result of specific combinations of metabolic and inflammatory cues, which drive distinct profibrotic paths in the glomeruli and the tubulointerstitial compartments. These findings, which found confirmation in tissue-based quantitative immune-phenotyping of transplanted kidney biopsies, indicate that the combination of in vitro and in silico modeling represents a powerful systems medicine approach to dissect fibrosis pathogenesis and develop coordinated targeted approaches.

scholarly journals Plasmacytoid Dendritic Cells Regulate Autoreactive B Cell Activation via Soluble Factors and in a Cell-to-Cell Contact Manner

2009 ◽  
Vol 183 (11) ◽  
pp. 7140-7149 ◽  
Author(s):  
Chuanlin Ding ◽  
Yihua Cai ◽  
Jose Marroquin ◽  
Suzanne T. Ildstad ◽  
Jun Yan
Keyword(s):  
Dendritic Cells ◽  
B Cell ◽  
Cell Activation ◽  
Plasmacytoid Dendritic Cells ◽  
Cell Contact ◽  
B Cell Activation ◽  
Soluble Factors ◽  
A Cell

scholarly journals Nondestructive nanostraw intracellular sampling for longitudinal cell monitoring

2017 ◽  
Vol 114 (10) ◽  
pp. E1866-E1874 ◽  
Author(s):  
Yuhong Cao ◽  
Martin Hjort ◽  
Haodong Chen ◽  
Fikri Birey ◽  
Sergio A. Leal-Ortiz ◽  
...  
Keyword(s):  
Cell Types ◽  
Cell Extract ◽  
Cell Contact ◽  
Time Resolved ◽  
Induced Pluripotency ◽  
Native Cell ◽  
Dynamic Cell ◽  
Cell Monitoring ◽  
A Cell ◽  
Induced Pluripotent

Here, we report a method for time-resolved, longitudinal extraction and quantitative measurement of intracellular proteins and mRNA from a variety of cell types. Cytosolic contents were repeatedly sampled from the same cell or population of cells for more than 5 d through a cell-culture substrate, incorporating hollow 150-nm-diameter nanostraws (NS) within a defined sampling region. Once extracted, the cellular contents were analyzed with conventional methods, including fluorescence, enzymatic assays (ELISA), and quantitative real-time PCR. This process was nondestructive with >95% cell viability after sampling, enabling long-term analysis. It is important to note that the measured quantities from the cell extract were found to constitute a statistically significant representation of the actual contents within the cells. Of 48 mRNA sequences analyzed from a population of cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs), 41 were accurately quantified. The NS platform samples from a select subpopulation of cells within a larger culture, allowing native cell-to-cell contact and communication even during vigorous activity such as cardiomyocyte beating. This platform was applied both to cell lines and to primary cells, including CHO cells, hiPSC-CMs, and human astrocytes derived in 3D cortical spheroids. By tracking the same cell or group of cells over time, this method offers an avenue to understand dynamic cell behavior, including processes such as induced pluripotency and differentiation.

Dendritic cells of the human epidermis: immuno-electron microscopic studies of la antigen reactivity

1978 ◽  
Vol 36 (2) ◽  
pp. 644-645
Author(s):  
G. Rowden ◽  
M. G. Lewis ◽  
T. M. Phillips
Keyword(s):  
Dendritic Cells ◽  
Langerhans Cells ◽  
Cell Types ◽  
Cell Type ◽  
Electron Microscopic ◽  
La Antigen ◽  
Microscopic Studies ◽  
A Cell ◽  
C3 Receptors ◽  
Antigen Reactivity

Langerhans cells of mammalian stratified squamous epithelial have proven to be an enigma since their discovery in 1868. These dendritic suprabasal cells have been considered as related to melanocytes either as effete cells, or as post divisional products. Although grafting experiments seemed to demonstrate the independence of the cell types, much confusion still exists. The presence in the epidermis of a cell type with morphological features seemingly shared by melanocytes and Langerhans cells has been especially troublesome. This so called "indeterminate", or " -dendritic cell" lacks both Langerhans cells granules and melanosomes, yet it is clearly not a keratinocyte. Suggestions have been made that it is related to either Langerhans cells or melanocyte. Recent studies have unequivocally demonstrated that Langerhans cells are independent cells with immune function. They display Fc and C3 receptors on their surface as well as la (immune region associated) antigens.

CD38 as an immunomodulator in cancer

2020 ◽  
Vol 16 (34) ◽  
pp. 2853-2861
Author(s):  
Yanli Li ◽  
Rui Yang ◽  
Limo Chen ◽  
Sufang Wu
Keyword(s):  
Multiple Myeloma ◽  
Cell Activation ◽  
Human Tissues ◽  
Transmembrane Glycoprotein ◽  
Cell Activation Marker ◽  
Research Findings ◽  
A Cell ◽  
And Function ◽  
Human Molecule

CD38 is a transmembrane glycoprotein that is widely expressed in a variety of human tissues and cells, especially those in the immune system. CD38 protein was previously considered as a cell activation marker, and today monoclonal antibodies targeting CD38 have witnessed great achievements in multiple myeloma and promoted researchers to conduct research on other tumors. In this review, we provide a wide-ranging review of the biology and function of the human molecule outside the field of myeloma. We focus mainly on current research findings to summarize and update the findings gathered from diverse areas of study. Based on these findings, we attempt to extend the role of CD38 in the context of therapy of solid tumors and expand the role of the molecule from a simple marker to an immunomodulator.

scholarly journals EMeth: An EM algorithm for cell type decomposition based on DNA methylation data

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hanyu Zhang ◽  
Ruoyi Cai ◽  
James Dai ◽  
Wei Sun
Keyword(s):  
Dna Methylation ◽  
Tumor Cells ◽  
T Regulatory Cells ◽  
Simulated Data ◽  
Cell Types ◽  
Computational Method ◽  
Methylation Data ◽  
Cell Type ◽  
A Cell ◽  
Type Decomposition

AbstractWe introduce a new computational method named EMeth to estimate cell type proportions using DNA methylation data. EMeth is a reference-based method that requires cell type-specific DNA methylation data from relevant cell types. EMeth improves on the existing reference-based methods by detecting the CpGs whose DNA methylation are inconsistent with the deconvolution model and reducing their contributions to cell type decomposition. Another novel feature of EMeth is that it allows a cell type with known proportions but unknown reference and estimates its methylation. This is motivated by the case of studying methylation in tumor cells while bulk tumor samples include tumor cells as well as other cell types such as infiltrating immune cells, and tumor cell proportion can be estimated by copy number data. We demonstrate that EMeth delivers more accurate estimates of cell type proportions than several other methods using simulated data and in silico mixtures. Applications in cancer studies show that the proportions of T regulatory cells estimated by DNA methylation have expected associations with mutation load and survival time, while the estimates from gene expression miss such associations.

scholarly journals Tim-3 enhances FcεRI-proximal signaling to modulate mast cell activation

2015 ◽  
Vol 212 (13) ◽  
pp. 2289-2304 ◽  
Author(s):  
Binh L. Phong ◽  
Lyndsay Avery ◽  
Tina L. Sumpter ◽  
Jacob V. Gorman ◽  
Simon C. Watkins ◽  
...  
Keyword(s):  
T Cells ◽  
Mast Cell ◽  
Signaling Pathways ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Late Phase ◽  
Cell Types ◽  
Mast Cell Activation ◽  
Positive Role ◽  
Ample Evidence

T cell (or transmembrane) immunoglobulin and mucin domain protein 3 (Tim-3) has attracted significant attention as a novel immune checkpoint receptor (ICR) on chronically stimulated, often dysfunctional, T cells. Antibodies to Tim-3 can enhance antiviral and antitumor immune responses. Tim-3 is also constitutively expressed by mast cells, NK cells and specific subsets of macrophages and dendritic cells. There is ample evidence for a positive role for Tim-3 in these latter cell types, which is at odds with the model of Tim-3 as an inhibitory molecule on T cells. At this point, little is known about the molecular mechanisms by which Tim-3 regulates the function of T cells or other cell types. We have focused on defining the effects of Tim-3 ligation on mast cell activation, as these cells constitutively express Tim-3 and are activated through an ITAM-containing receptor for IgE (FcεRI), using signaling pathways analogous to those in T cells. Using a variety of gain- and loss-of-function approaches, we find that Tim-3 acts at a receptor-proximal point to enhance Lyn kinase-dependent signaling pathways that modulate both immediate-phase degranulation and late-phase cytokine production downstream of FcεRI ligation.

scholarly journals Adhesive multiplicity in the interaction of embryonic fibroblasts and myoblasts with extracellular matrices.

1984 ◽  
Vol 99 (4) ◽  
pp. 1398-1404 ◽  
Author(s):  
C Decker ◽  
R Greggs ◽  
K Duggan ◽  
J Stubbs ◽  
A Horwitz
Keyword(s):  
Skeletal Muscle ◽  
Cardiac Muscle ◽  
Cardiac Fibroblasts ◽  
Cell Types ◽  
Extracellular Matrices ◽  
Common Denominator ◽  
Cell Matrix ◽  
Skeletal Myoblasts ◽  
A Cell ◽  
Cell Matrix Adhesion

Neff et al. (1982, J. Cell Biol., 95:654-666) have described a monoclonal antibody, CSAT, directed against a cell surface antigen that participates in the adhesion of skeletal muscle to extracellular matrices. We used the same antibody to compare and parse the determinants of adhesion and morphology on myogenic and fibrogenic cells. We report here that the antigen is present on skeletal and cardiac muscle and on tendon, skeletal, dermal, and cardiac fibroblasts; however, its contribution to their morphology and adhesion is different. The antibody produces large alterations in the morphology and adhesion of skeletal myoblasts and tendon fibroblasts; in contrast, its effects on the cardiac fibroblasts are not readily detected. The effects of CSAT on the other cell types, i.e., dermal and skeletal fibroblasts, cardiac muscle, 5-bromodeoxyuridine-treated skeletal muscle, lie between these extremes. The effects of CSAT on the skeletal myoblasts depends on the calcium concentration in the growth medium and on the culture age. We interpret these differential responses to CSAT as revealing differences in the adhesion of the various cells to extracellular matrices. This interpretation is supported by parallel studies using quantitative assays of cell-matrix adhesion. The likely origin of these adhesive differences is the progressive display of different kinds of adhesion-related molecules and their organizational complexes on increasingly adhesive cells. The antigen to which CSAT is directed is present on all of the above cells and thus appears to be a lowest common denominator of their adhesion to extracellular matrices.

scholarly journals Urinary Extracellular Vesicles: Uncovering the Basis of the Pathological Processes in Kidney-Related Diseases

2021 ◽  
Vol 22 (12) ◽  
pp. 6507
Author(s):  
Giulia Cricrì ◽  
Linda Bellucci ◽  
Giovanni Montini ◽  
Federica Collino
Keyword(s):  
Extracellular Vesicles ◽  
Cell Types ◽  
Diagnostic Techniques ◽  
Cell Contact ◽  
Glomerular Filtration Barrier ◽  
Alternative Source ◽  
Filtration Barrier ◽  
Multicellular Interactions ◽  
Almost All ◽  
Cell Crosstalk

Intercellular communication governs multicellular interactions in complex organisms. A variety of mechanisms exist through which cells can communicate, e.g., cell-cell contact, the release of paracrine/autocrine soluble molecules, or the transfer of extracellular vesicles (EVs). EVs are membrane-surrounded structures released by almost all cell types, acting both nearby and distant from their tissue/organ of origin. In the kidney, EVs are potent intercellular messengers released by all urinary system cells and are involved in cell crosstalk, contributing to physiology and pathogenesis. Moreover, urine is a reservoir of EVs coming from the circulation after crossing the glomerular filtration barrier—or originating in the kidney. Thus, urine represents an alternative source for biomarkers in kidney-related diseases, potentially replacing standard diagnostic techniques, including kidney biopsy. This review will present an overview of EV biogenesis and classification and the leading procedures for isolating EVs from body fluids. Furthermore, their role in intra-nephron communication and their use as a diagnostic tool for precision medicine in kidney-related disorders will be discussed.

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