Distinct cell types control lymphoid subset development by means of IL-15 and IL-15 receptor   expression

AbstractUnderstanding how genes and experiences work in concert to generate phenotypic variability will provide a better understanding of individuality. Here, we considered this in the context of the main olfactory epithelium, a chemosensory structure with over a thousand distinct cell-types, in mice. We identified a subpopulation of at least three types of olfactory sensory neurons, defined by receptor expression, whose abundances were sexually dimorphic. This subpopulation of olfactory sensory neurons was over-represented in sex-separated female mice and responded robustly to the male-specific semiochemicals 2-sec-butyl-4,5-dihydrothaizole and (methylthio)methanethiol. Sex-combined housing led to a robust attenuation of the female over-representation. Testing of Bax null mice revealed a Bax-dependence in generating the sexual dimorphism in sex-separated mice. Altogether, our results suggest a profound role of experience in influencing homeostatic neural lifespan mechanisms to generate a robust sexually dimorphic phenotype in the main olfactory epithelium.

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Semiochemical responsive olfactory sensory neurons are sexually dimorphic and plastic

eLife ◽

10.7554/elife.54501 ◽

2020 ◽

Vol 9 ◽

Author(s):

Aashutosh Vihani ◽

Xiaoyang Serene Hu ◽

Sivaji Gundala ◽

Sachiko Koyama ◽

Eric Block ◽

...

Keyword(s):

Sensory Neurons ◽

Olfactory Epithelium ◽

Phenotypic Variability ◽

Cell Types ◽

Receptor Expression ◽

Olfactory Sensory Neurons ◽

Sexually Dimorphic ◽

Sequencing Analysis ◽

Main Olfactory Epithelium ◽

Distinct Cell

Understanding how genes and experience work in concert to generate phenotypic variability will provide a better understanding of individuality. Here, we considered this in the main olfactory epithelium, a chemosensory structure with over a thousand distinct cell types in mice. We identified a subpopulation of olfactory sensory neurons, defined by receptor expression, whose abundances were sexually dimorphic. This subpopulation of olfactory sensory neurons was over-represented in sex-separated mice and robustly responsive to sex-specific semiochemicals. Sex-combined housing led to an attenuation of the dimorphic representations. Single-cell sequencing analysis revealed an axis of activity-dependent gene expression amongst a subset of the dimorphic OSN populations. Finally, the pro-apoptotic gene Baxwas necessary to generate the dimorphic representations. Altogether, our results suggest a role of experience and activity in influencing homeostatic mechanisms to generate a robust sexually dimorphic phenotype in the main olfactory epithelium.

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Fine Structure of the Malpighian Tubules of the Mosquito, Culex pipiens

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010006605x ◽

1971 ◽

Vol 29 ◽

pp. 402-403

Author(s):

Brendan Clifford

Keyword(s):

Fine Structure ◽

Culex Pipiens ◽

Stellate Cell ◽

Malpighian Tubule ◽

Cell Types ◽

Instar Larva ◽

Malpighian Tubules ◽

Calliphora Erythrocephala ◽

Distinct Cell ◽

Basal Plasma

An ultrastructural investigation of the Malpighian tubules of the fourth instar larva of Culex pipiens was undertaken as part of a continuing study of the fine structure of transport epithelia.Each of the five Malpighian tubules was found to be morphologically identical and regionally undifferentiated. Two distinct cell types, the primary and stellate, were found intermingled along the length of each tubule. The ultrastructure of the stellate cell was previously described in the Malpighian tubule of the blowfly, Calliphora erythrocephala by Berridge and Oschman.The basal plasma membrane of the primary cell is extremely irregular, giving rise to a complex interconnecting network of basal channels. The compartments of cytoplasm entrapped within this system of basal infoldings contain mitochondria, free ribosomes, and small amounts of rough endoplasmic reticulum. The mitochondria are distinctive in that the cristae run parallel to the long axis of the organelle.

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Role of the 807 C/T Polymorphism of the α2 Gene in Platelet GP Ia Collagen Receptor Expression and Function

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614605 ◽

1999 ◽

Vol 81 (06) ◽

pp. 951-956 ◽

Cited By ~ 59

Author(s):

J. Corral ◽

R. González-Conejero ◽

J. Rivera ◽

F. Ortuño ◽

P. Aparicio ◽

...

Keyword(s):

Venous Thrombosis ◽

Cell Types ◽

Receptor Expression ◽

Case Control Studies ◽

Platelet Surface ◽

Vitro Analysis ◽

And Function ◽

In Vitro Analysis

SummaryThe variability of the platelet GP Ia/IIa density has been associated with the 807 C/T polymorphism (Phe 224) of the GP Ia gene in American Caucasian population. We have investigated the genotype and allelic frequencies of this polymorphism in Spanish Caucasians. The T allele was found in 35% of the 284 blood donors analyzed. We confirmed in 159 healthy subjects a significant association between the 807 C/T polymorphism and the platelet GP Ia density. The T allele correlated with high number of GP Ia molecules on platelet surface. In addition, we observed a similar association of this polymorphism with the expression of this protein in other blood cell types. The platelet responsiveness to collagen was determined by “in vitro” analysis of the platelet activation and aggregation response. We found no significant differences in these functional platelet parameters according to the 807 C/T genotype. Finally, results from 3 case/control studies involving 302 consecutive patients (101 with coronary heart disease, 104 with cerebrovascular disease and 97 with deep venous thrombosis) determined that the 807 C/T polymorphism of the GP Ia gene does not represent a risk factor for arterial or venous thrombosis.

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Metabolic activation and colitis pathogenesis is prevented by lymphotoxin β receptor expression in neutrophils

Mucosal Immunology ◽

10.1038/s41385-021-00378-7 ◽

2021 ◽

Author(s):

Thomas Riffelmacher ◽

Daniel A. Giles ◽

Sonja Zahner ◽

Martina Dicker ◽

Alexander Y. Andreyev ◽

...

Keyword(s):

Severe Disease ◽

Metabolic Activation ◽

Cell Types ◽

Receptor Expression ◽

Neutrophil Accumulation ◽

Functional Studies ◽

Mitochondrial Ros ◽

Tnf Superfamily ◽

Β Receptor ◽

Lymphotoxin Beta Receptor

AbstractInflammatory bowel disease is characterized by an exacerbated intestinal immune response, but the critical mechanisms regulating immune activation remain incompletely understood. We previously reported that the TNF-superfamily molecule TNFSF14 (LIGHT) is required for preventing severe disease in mouse models of colitis. In addition, deletion of lymphotoxin beta receptor (LTβR), which binds LIGHT, also led to aggravated colitis pathogenesis. Here, we aimed to determine the cell type(s) requiring LTβR and the mechanism critical for exacerbation of colitis. Specific deletion of LTβR in neutrophils (LTβRΔN), but not in several other cell types, was sufficient to induce aggravated colitis and colonic neutrophil accumulation. Mechanistically, RNA-Seq analysis revealed LIGHT-induced suppression of cellular metabolism, and mitochondrial function, that was dependent on LTβR. Functional studies confirmed increased mitochondrial mass and activity, associated with excessive mitochondrial ROS production and elevated glycolysis at steady-state and during colitis. Targeting these metabolic changes rescued exacerbated disease severity. Our results demonstrate that LIGHT signals to LTβR on neutrophils to suppress metabolic activation and thereby prevents exacerbated immune pathogenesis during colitis.

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NF-κB in Cancer Immunity: Friend or Foe?

Cells ◽

10.3390/cells10020355 ◽

2021 ◽

Vol 10 (2) ◽

pp. 355

Author(s):

Guilhem Lalle ◽

Julie Twardowski ◽

Yenkel Grinberg-Bleyer

Keyword(s):

Immune Responses ◽

Therapeutic Potential ◽

Cell Types ◽

Transcriptional Activators ◽

New Class ◽

Complex Interactions ◽

Cancer Immunity ◽

Distinct Cell ◽

Cancer Initiation ◽

Cancer Outcome

The emergence of immunotherapies has definitely proven the tight relationship between malignant and immune cells, its impact on cancer outcome and its therapeutic potential. In this context, it is undoubtedly critical to decipher the transcriptional regulation of these complex interactions. Following early observations demonstrating the roles of NF-κB in cancer initiation and progression, a series of studies converge to establish NF-κB as a master regulator of immune responses to cancer. Importantly, NF-κB is a family of transcriptional activators and repressors that can act at different stages of cancer immunity. In this review, we provide an overview of the selective cell-intrinsic contributions of NF-κB to the distinct cell types that compose the tumor immune environment. We also propose a new view of NF-κB targeting drugs as a new class of immunotherapies for cancer.

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Glucocorticoid Receptor β (GRβ): Beyond Its Dominant-Negative Function

International Journal of Molecular Sciences ◽

10.3390/ijms22073649 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3649

Author(s):

Patricia Ramos-Ramírez ◽

Omar Tliba

Keyword(s):

Current Knowledge ◽

Inflammatory Diseases ◽

Cell Communication ◽

Cell Types ◽

The Body ◽

Dominant Negative ◽

Negative Effects ◽

Independent Manner ◽

Distinct Cell ◽

Induced Apoptosis

Glucocorticoids (GCs) act via the GC receptor (GR), a receptor ubiquitously expressed in the body where it drives a broad spectrum of responses within distinct cell types and tissues, which vary in strength and specificity. The variability of GR-mediated cell responses is further extended by the existence of GR isoforms, such as GRα and GRβ, generated through alternative splicing mechanisms. While GRα is the classic receptor responsible for GC actions, GRβ has been implicated in the impairment of GRα-mediated activities. Interestingly, in contrast to the popular belief that GRβ actions are restricted to its dominant-negative effects on GRα-mediated responses, GRβ has been shown to have intrinsic activities and “directly” regulates a plethora of genes related to inflammatory process, cell communication, migration, and malignancy, each in a GRα-independent manner. Furthermore, GRβ has been associated with increased cell migration, growth, and reduced sensitivity to GC-induced apoptosis. We will summarize the current knowledge of GRβ-mediated responses, with a focus on the GRα-independent/intrinsic effects of GRβ and the associated non-canonical signaling pathways. Where appropriate, potential links to airway inflammatory diseases will be highlighted.

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Development, characterization, and applications of multi-material stereolithography bioprinting

Scientific Reports ◽

10.1038/s41598-021-82102-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Bagrat Grigoryan ◽

Daniel W. Sazer ◽

Amanda Avila ◽

Jacob L. Albritton ◽

Aparna Padhye ◽

...

Keyword(s):

Material Selection ◽

Cell Types ◽

Fluorescent Tracers ◽

Regional Feature ◽

Multicellular Aggregates ◽

Distinct Cell ◽

Adenocarcinoma Cells ◽

Mammalian Tissues ◽

Heterotypic Interactions ◽

Feature Alignment

AbstractAs a 3D bioprinting technique, hydrogel stereolithography has historically been limited in its ability to capture the spatial heterogeneity that permeates mammalian tissues and dictates structure–function relationships. This limitation stems directly from the difficulty of preventing unwanted material mixing when switching between different liquid bioinks. Accordingly, we present the development, characterization, and application of a multi-material stereolithography bioprinter that provides controlled material selection, yields precise regional feature alignment, and minimizes bioink mixing. Fluorescent tracers were first used to highlight the broad design freedoms afforded by this fabrication strategy, complemented by morphometric image analysis to validate architectural fidelity. To evaluate the bioactivity of printed gels, 344SQ lung adenocarcinoma cells were printed in a 3D core/shell architecture. These cells exhibited native phenotypic behavior as evidenced by apparent proliferation and formation of spherical multicellular aggregates. Cells were also printed as pre-formed multicellular aggregates, which appropriately developed invasive protrusions in response to hTGF-β1. Finally, we constructed a simplified model of intratumoral heterogeneity with two separate sub-populations of 344SQ cells, which together grew over 14 days to form a dense regional interface. Together, these studies highlight the potential of multi-material stereolithography to probe heterotypic interactions between distinct cell types in tissue-specific microenvironments.

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