scholarly journals Lrig1 and Wnt dependent niches dictate segregation of resident immune cells and melanocytes in murine tail epidermis

2021 ◽  
Author(s):  
Susanne C. Baess ◽  
Annika Graband ◽  
Kristin Sere ◽  
Martin Zenke ◽  
Catherin Niemann ◽  
...  
Keyword(s):  
Host Defense ◽  
Immune Cells ◽  
Langerhans Cells ◽  
Immune Surveillance ◽  
Cell Types ◽  
First Line ◽  
Interfollicular Epidermis ◽  
Canonical Wnt ◽  
Cellular Hierarchy ◽  
Surveillance Analysis

The barrier-forming, self-renewing mammalian epidermis comprises keratinocytes, pigment-producing melanocytes, and resident immune cells as first-line host defense. In murine tail skin, interfollicular epidermis patterns into pigmented ′scale′ and non-pigmented ′interscale′ epidermis. Why and how mature melanocytes confine to scale epidermis is unresolved. Here, we delineate a cellular hierarchy among epidermal cell types that determines skin patterning. Already during postnatal development, melanocytes co-segregate with newly forming scale compartments. Intriguingly, this process coincides with partitioning of both Langerhans cells and dendritic epidermal T-cells to interscale epidermis, suggesting functional segregation of pigmentation and immune surveillance. Analysis of non-pigmented mice and of mice lacking melanocytes or resident immune cells revealed that immunocyte patterning is melanocyte- and melanin-independent, and, vice versa, immune cells do not control melanocyte localization. Instead, genetically enforced progressive scale fusion upon Lrig1 deletion showed that melanocytes and immune cells dynamically follow epithelial scale:interscale patterns. Importantly, disrupting Wnt-Lef1 function in keratinocytes caused melanocyte mislocalization to interscale epidermis, implicating canonical Wnt signaling in organizing the pigmentation pattern. Together, this work uncovered cellular and molecular principles underlying the compartmentalization of tissue functions in skin.

scholarly journals Host Defense and the Airway Epithelium: Frontline Responses That Protect against Bacterial Invasion and Pneumonia

2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
Nicholas A. Eisele ◽  
Deborah M. Anderson
Keyword(s):  
Epithelial Cells ◽  
Host Defense ◽  
Immune Cells ◽  
Airway Epithelium ◽  
Inflammatory Cells ◽  
Airway Epithelial Cells ◽  
Bacterial Invasion ◽  
Airway Epithelial ◽  
First Line ◽  
Protein Matrices

Airway epithelial cells are the first line of defense against invading microbes, and they protect themselves through the production of carbohydrate and protein matrices concentrated with antimicrobial products. In addition, they act as sentinels, expressing pattern recognition receptors that become activated upon sensing bacterial products and stimulate downstream recruitment and activation of immune cells which clear invading microbes. Bacterial pathogens that successfully colonize the lungs must resist these mechanisms or inhibit their production, penetrate the epithelial barrier, and be prepared to resist a barrage of inflammation. Despite the enormous task at hand, relatively few virulence factors coordinate the battle with the epithelium while simultaneously providing resistance to inflammatory cells and causing injury to the lung. Here we review mechanisms whereby airway epithelial cells recognize pathogens and activate a program of antibacterial pathways to prevent colonization of the lung, along with a few examples of how bacteria disrupt these responses to cause pneumonia.

scholarly journals Can cancer GWAS variants modulate immune cells in the tumor microenvironment?

2018 ◽  
Author(s):  
Yi Zhang ◽  
Mohith Manjunath ◽  
Jialu Yan ◽  
Brittany A. Baur ◽  
Shilu Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Cells ◽  
Cancer Susceptibility ◽  
Association Studies ◽  
Immune Surveillance ◽  
Tumor Infiltrating Lymphocytes ◽  
Cell Types ◽  
Potential Effect ◽  
Chromatin Interaction ◽  
Genome Wide Association Studies

AbstractGenome-wide association studies (GWAS) have hitherto identified several genetic variants associated with cancer susceptibility, but the molecular functions of these risk modulators remain largely uncharacterized. Recent studies have begun to uncover the regulatory potential of non-coding GWAS SNPs by using epigenetic information in corresponding cancer cell types and matched normal tissues. However, this approach does not explore the potential effect of risk germline variants on other important cell types that constitute the microenvironment of tumor or its precursor. This paper presents evidence that the breast cancer-associated variant rs3903072 may regulate the expression of CTSW in tumor infiltrating lymphocytes. CTSW is a candidate tumor-suppressor gene, with expression highly specific to immune cells and also positively correlated with breast cancer patient survival. Integrative analyses suggest a putative causative variant in a GWAS-linked enhancer in lymphocytes that loops to the 3’ end of CTSW through three-dimensional chromatin interaction. Our work thus poses the possibility that a cancer-associated genetic variant might regulate a gene not only in the cell of cancer origin, but also in immune cells in the microenvironment, thereby modulating the immune surveillance by T lymphocytes and natural killer cells and affecting the clearing of early cancer initiating cells.

scholarly journals Cytosolic and nuclear recognition of virus and viral evasion

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Siji Li ◽  
Lili Cao ◽  
Zeming Zhang ◽  
Ming Kuang ◽  
Luoying Chen ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Host Defense ◽  
Innate Immune System ◽  
Recent Progress ◽  
Immune Surveillance ◽  
Innate Immune ◽  
First Line ◽  
Innate Recognition ◽  
Replication Intermediates ◽  
Host Immune Surveillance

AbstractThe innate immune system is the first line of host defense, which responds rapidly to viral infection. Innate recognition of viruses is mediated by a set of pattern recognition receptors (PRRs) that sense viral genomic nucleic acids and/or replication intermediates. PRRs are mainly localized either to the endosomes, the plasma membrane or the cytoplasm. Recent evidence suggested that several proteins located in the nucleus could also act as viral sensors. In turn, these important elements are becoming the target for most viruses to evade host immune surveillance. In this review, we focus on the recent progress in the study of viral recognition and evasion.

scholarly journals Neutrophils in Streptococcus suis Infection: From Host Defense to Pathology

2021 ◽  
Vol 9 (11) ◽  
pp. 2392
Author(s):  
Marêva Bleuzé ◽  
Marcelo Gottschalk ◽  
Mariela Segura
Keyword(s):  
Host Defense ◽  
Immune Cells ◽  
Immune Surveillance ◽  
Clinical Manifestations ◽  
Streptococcus Suis ◽  
Cellular Level ◽  
Economic Losses ◽  
Cell Type ◽  
Swine Pathogen

Streptococcus suis is a swine pathogen and zoonotic agent responsible for economic losses to the porcine industry. Infected animals may develop meningitis, arthritis, endocarditis, sepsis and/or sudden death. The pathogenesis of the infection implies that bacteria breach mucosal host barriers and reach the bloodstream, where they escape immune-surveillance mechanisms and spread throughout the organism. The clinical manifestations are mainly the consequence of an exacerbated inflammation, defined by an exaggerated production of cytokines and recruitment of immune cells. Among them, neutrophils arrive first in contact with the pathogens to combat the infection. Neutrophils initiate and maintain inflammation, by producing cytokines and deploying their arsenal of antimicrobial mechanisms. Furthermore, neutrophilic leukocytosis characterizes S. suis infection, and lesions of infected subjects contain a large number of neutrophils. Therefore, this cell type may play a role in host defense and/or in the exacerbated inflammation. Nevertheless, a limited number of studies addressed the role or functions of neutrophils in the context of S. suis infection. In this review, we will explore the literature about S. suis and neutrophils, from their interaction at a cellular level, to the roles and behaviors of neutrophils in the infected host in vivo.

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.

scholarly journals Single-cell map of diverse immune phenotypes in the acute myeloid leukemia microenvironment

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Rongqun Guo ◽  
Mengdie Lü ◽  
Fujiao Cao ◽  
Guanghua Wu ◽  
Fengcai Gao ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Single Cell ◽  
Myeloid Leukemia ◽  
Immune Cell ◽  
Immune Surveillance ◽  
Cell Types ◽  
Developmental Trajectory ◽  
Significant Difference ◽  
Cell Phenotypes ◽  
Acute Myeloid

Abstract Background Knowledge of immune cell phenotypes, function, and developmental trajectory in acute myeloid leukemia (AML) microenvironment is essential for understanding mechanisms of evading immune surveillance and immunotherapy response of targeting special microenvironment components. Methods Using a single-cell RNA sequencing (scRNA-seq) dataset, we analyzed the immune cell phenotypes, function, and developmental trajectory of bone marrow (BM) samples from 16 AML patients and 4 healthy donors, but not AML blasts. Results We observed a significant difference between normal and AML BM immune cells. Here, we defined the diversity of dendritic cells (DC) and macrophages in different AML patients. We also identified several unique immune cell types including T helper cell 17 (TH17)-like intermediate population, cytotoxic CD4+ T subset, T cell: erythrocyte complexes, activated regulatory T cells (Treg), and CD8+ memory-like subset. Emerging AML cells remodels the BM immune microenvironment powerfully, leads to immunosuppression by accumulating exhausted/dysfunctional immune effectors, expending immune-activated types, and promoting the formation of suppressive subsets. Conclusion Our results provide a comprehensive AML BM immune cell census, which can help to select pinpoint targeted drug and predict efficacy of immunotherapy.

scholarly journals Multifaceted Functions of Platelets in Cancer: From Tumorigenesis to Liquid Biopsy Tool and Drug Delivery System

2020 ◽  
Vol 21 (24) ◽  
pp. 9585
Author(s):  
Melania Dovizio ◽  
Patrizia Ballerini ◽  
Rosa Fullone ◽  
Stefania Tacconelli ◽  
Annalisa Contursi ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cancer Cells ◽  
Immune Cells ◽  
Expression Patterns ◽  
Cell Communication ◽  
Antiplatelet Agents ◽  
Cell Types ◽  
Disease Monitoring ◽  
Crucial Component ◽  
Numerous Cell

Platelets contribute to several types of cancer through plenty of mechanisms. Upon activation, platelets release many molecules, including growth and angiogenic factors, lipids, and extracellular vesicles, and activate numerous cell types, including vascular and immune cells, fibroblasts, and cancer cells. Hence, platelets are a crucial component of cell–cell communication. In particular, their interaction with cancer cells can enhance their malignancy and facilitate the invasion and colonization of distant organs. These findings suggest the use of antiplatelet agents to restrain cancer development and progression. Another peculiarity of platelets is their capability to uptake proteins and transcripts from the circulation. Thus, cancer-patient platelets show specific proteomic and transcriptomic expression patterns, a phenomenon called tumor-educated platelets (TEP). The transcriptomic/proteomic profile of platelets can provide information for the early detection of cancer and disease monitoring. Platelet ability to interact with tumor cells and transfer their molecular cargo has been exploited to design platelet-mediated drug delivery systems to enhance the efficacy and reduce toxicity often associated with traditional chemotherapy. Platelets are extraordinary cells with many functions whose exploitation will improve cancer diagnosis and treatment.

scholarly journals Characterization of epithelial cells, connective tissue cells and immune cells in human upper airway mucosa by immunofluorescence multichannel image cytometry: a pilot study

2020 ◽  
Author(s):  
Aris I. Giotakis ◽  
Jozsef Dudas ◽  
Rudolf Glueckert ◽  
Daniel Dejaco ◽  
Julia Ingruber ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Chronic Rhinosinusitis ◽  
Immune Cells ◽  
Upper Airway ◽  
Image Cytometry ◽  
Cell Types ◽  
Epithelial Layer ◽  
Double Positive ◽  
Airway Mucosa ◽  
Single Positive

AbstractEpithelial, connective tissue and immune cells contribute in various ways to the pathophysiology of chronic rhinosinusitis (CRS). However, data of their distribution in upper airway mucosa are sparse. We aimed to provide quantitative, purely informative data on the distribution of these cell lineages and their coexpression patterns, which might help identifying, e.g., cells in the epithelium undergoing through epithelial–mesenchymal transition (EMT). For this purpose, we used immunofluorescence multichannel image cytometry (IMIC). We examined fixed paraffin-embedded tissue samples (FFPE) of six patients with chronic rhinosinusitis (CRS) and of three patients without CRS (controls). The direct-conjugated antibodies pancytokeratin, vimentin and CD45/CD18 were used for coexpression analysis in epithelial layer and lamina propria. Image acquisition and analysis were performed with TissueFAXS and StrataQuest, respectively. To distinguish positive from negative expression, a ratio between cell-specific immunostaining intensity and background was developed. Isotype controls were used as negative controls. Per patient, a 4.5-mm2 tissue area was scanned and a median of 14,875 cells was recognized. The most common cell types were cytokeratin-single-positive (26%), vimentin-single-positive (13%) and CD45/CD18-single-positive with CD45/CD18–vimentin-double-positive cells (29%). In the patients with CRS, CD45/CD18-single-positive cells were 3–6 times higher compared to the control patients. In the epithelial layer, cytokeratin–vimentin-double-positive EMT cells were observed 3–5 times higher in the patients with CRS than in the control patients. This study provided quantitative data for the distribution of crucial cell types in CRS. Future studies may focus on the distribution and coexpression patterns of different immune cells in CRS or even cancer tissue.

The Intersection of Metformin and Inflammation

2021 ◽  
Author(s):  
Leena P. Bharath ◽  
Barbara S. Nikolajczyk
Keyword(s):  
Mitochondrial Function ◽  
Immune Cells ◽  
Immune Cell ◽  
Cell Types ◽  
Remarkable Effect ◽  
Tumor Onset ◽  
Age Related ◽  
Immune Mediated ◽  
Autoimmune Conditions ◽  
Near Term

The biguanide metformin is the most commonly used antidiabetic drug. Recent studies show that metformin not only improves chronic inflammation by improving metabolic parameters but also has a direct anti-inflammatory effect. In light of these findings, it is essential to identify the inflammatory pathways targeted by metformin to develop a comprehensive understanding of the mechanisms of action of this drug. Commonly accepted mechanisms of metformin action include AMPK activation and inhibition of mTOR pathways, which are evaluated in multiple diseases. Additionally, metformin's action on mitochondrial function and cellular homeostasis processes such as autophagy, is of particular interest because of the importance of these mechanisms in maintaining cellular health. Both dysregulated mitochondria and failure of the autophagy pathways, the latter of which impair clearance of dysfunctional, damaged, or excess organelles, affect cellular health drastically and can trigger the onset of metabolic and age-related diseases. Immune cells are the fundamental cell types that govern the health of an organism. Thus, dysregulation of autophagy or mitochondrial function in immune cells has a remarkable effect on susceptibility to infections, response to vaccination, tumor onset, and the development of inflammatory and autoimmune conditions. Here we summarize the latest research on metformin's regulation of immune cell mitochondrial function and autophagy as evidence that new clinical trials on metformin with primary outcomes related to the immune system should be considered to treat immune-mediated diseases over the near term.

scholarly journals Toll-Like Receptor-Based Strategies for Cancer Immunotherapy

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Saghar Pahlavanneshan ◽  
Ali Sayadmanesh ◽  
Hamidreza Ebrahimiyan ◽  
Mohsen Basiri
Keyword(s):  
Cancer Immunotherapy ◽  
Immune Cells ◽  
Immune Cell ◽  
Cell Types ◽  
Genetically Engineered ◽  
Current Status ◽  
Tlr Signaling ◽  
Functional Roles ◽  
Immunotherapy Of Cancer ◽  
Signaling Components

Toll-like receptors (TLRs) are expressed and play multiple functional roles in a variety of immune cell types involved in tumor immunity. There are plenty of data on the pharmacological targeting of TLR signaling using agonist molecules that boost the antitumor immune response. A recent body of research has also demonstrated promising strategies for improving the cell-based immunotherapy methods by inducing TLR signaling. These strategies include systemic administration of TLR antagonist along with immune cell transfer and also genetic engineering of the immune cells using TLR signaling components to improve the function of genetically engineered immune cells such as chimeric antigen receptor-modified T cells. Here, we explore the current status of the cancer immunotherapy approaches based on manipulation of TLR signaling to provide a perspective of the underlying rationales and potential clinical applications. Altogether, reviewed publications suggest that TLRs make a potential target for the immunotherapy of cancer.

Sign in / Sign up

Export Citation Format

Share Document