scholarly journals A NKp80-based identification strategy reveals that CD56neg NK cells are not completely dysfunctional in health and disease

2020 ◽  
Author(s):  
Ane Orrantia ◽  
Iñigo Terrén ◽  
Alicia Izquierdo-Lafuente ◽  
Juncal A. Alonso-Cabrera ◽  
Victor Sandá ◽  
...  
Keyword(s):  
Nk Cells ◽  
Good Alternative ◽  
Specific Marker ◽  
Effector Functions ◽  
Multiparametric Flow Cytometry ◽  
Healthy Donors ◽  
A Cell ◽  
Health And Disease ◽  
Lineage Markers ◽  
Identification Strategy

ABSTRACTNatural killer (NK) cells are usually identified by the absence of other lineage markers, due to the lack of a cell surface specific marker. CD56neg NK cells, classically identified as CD56negCD16+ are known to be expanded in some pathological conditions. However, studies on CD56neg NK cells had revealed different results regarding the phenotype and functionality of these cells. This could be due to, among others, the unstable expression of CD16, which hinders CD56neg NK cells identification. Hence, we aim to determine an alternative surface marker to CD16 to better identify CD56neg NK cells. Using multiparametric flow cytometry, we have found that NKp80 is a good alternative to CD16 not only in healthy donors but also in HIV-1 infected subjects and multiple myeloma patients. Furthermore, we found differences between the functionality of CD56negNKp80+ and CD56negCD16+ NK cells both in healthy donors and patients, suggesting that the effector functions of CD56neg NK cells are not as diminished as previously thought. We proposed NKp80 as a noteworthy marker to identify and accurately re-characterize human CD56neg NK cells.

scholarly journals A NKp80-Based Identification Strategy Reveals that CD56neg NK Cells Are Not Completely Dysfunctional in Health and Disease

iScience ◽  
2020 ◽  
Vol 23 (7) ◽  
pp. 101298 ◽  
Author(s):  
Ane Orrantia ◽  
Iñigo Terrén ◽  
Alicia Izquierdo-Lafuente ◽  
Juncal A. Alonso-Cabrera ◽  
Victor Sandá ◽  
...  
Keyword(s):  
Nk Cells ◽  
Health And Disease ◽  
Identification Strategy

scholarly journals New tools for studying microglia in the mouse and human CNS

2016 ◽  
Vol 113 (12) ◽  
pp. E1738-E1746 ◽  
Author(s):  
Mariko L. Bennett ◽  
F. Chris Bennett ◽  
Shane A. Liddelow ◽  
Bahareh Ajami ◽  
Jennifer L. Zamanian ◽  
...  
Keyword(s):  
Transmembrane Protein ◽  
Surface Protein ◽  
Specific Marker ◽  
Developmental Origins ◽  
Cell Surface Protein ◽  
Immune Challenge ◽  
A Cell ◽  
Health And Disease ◽  
Brain And Spinal Cord ◽  
The Brain

The specific function of microglia, the tissue resident macrophages of the brain and spinal cord, has been difficult to ascertain because of a lack of tools to distinguish microglia from other immune cells, thereby limiting specific immunostaining, purification, and manipulation. Because of their unique developmental origins and predicted functions, the distinction of microglia from other myeloid cells is critically important for understanding brain development and disease; better tools would greatly facilitate studies of microglia function in the developing, adult, and injured CNS. Here, we identify transmembrane protein 119 (Tmem119), a cell-surface protein of unknown function, as a highly expressed microglia-specific marker in both mouse and human. We developed monoclonal antibodies to its intracellular and extracellular domains that enable the immunostaining of microglia in histological sections in healthy and diseased brains, as well as isolation of pure nonactivated microglia by FACS. Using our antibodies, we provide, to our knowledge, the first RNAseq profiles of highly pure mouse microglia during development and after an immune challenge. We used these to demonstrate that mouse microglia mature by the second postnatal week and to predict novel microglial functions. Together, we anticipate these resources will be valuable for the future study and understanding of microglia in health and disease.

scholarly journals The Role of the Cytoskeleton in Regulating the Natural Killer Cell Immune Response in Health and Disease: From Signaling Dynamics to Function

2021 ◽  
Vol 9 ◽  
Author(s):  
Aviad Ben-Shmuel ◽  
Batel Sabag ◽  
Guy Biber ◽  
Mira Barda-Saad
Keyword(s):  
Immune Response ◽  
Nk Cells ◽  
Signaling Pathways ◽  
Natural Killer ◽  
Immunological Synapse ◽  
Nk Cell ◽  
Cell Immune Response ◽  
Effector Functions ◽  
Health And Disease

Natural killer (NK) cells are innate lymphoid cells, which play key roles in elimination of virally infected and malignant cells. The balance between activating and inhibitory signals derived from NK surface receptors govern the NK cell immune response. The cytoskeleton facilitates most NK cell effector functions, such as motility, infiltration, conjugation with target cells, immunological synapse assembly, and cytotoxicity. Though many studies have characterized signaling pathways that promote actin reorganization in immune cells, it is not completely clear how particular cytoskeletal architectures at the immunological synapse promote effector functions, and how cytoskeletal dynamics impact downstream signaling pathways and activation. Moreover, pioneering studies employing advanced imaging techniques have only begun to uncover the architectural complexity dictating the NK cell activation threshold; it is becoming clear that a distinct organization of the cytoskeleton and signaling receptors at the NK immunological synapse plays a decisive role in activation and tolerance. Here, we review the roles of the actin cytoskeleton in NK cells. We focus on how actin dynamics impact cytolytic granule secretion, NK cell motility, and NK cell infiltration through tissues into inflammatory sites. We will also describe the additional cytoskeletal components, non-muscle Myosin II and microtubules that play pivotal roles in NK cell activity. Furthermore, special emphasis will be placed on the role of the cytoskeleton in assembly of immunological synapses, and how mutations or downregulation of cytoskeletal accessory proteins impact NK cell function in health and disease.

scholarly journals Maturation of the Na,K-ATPase in the Endoplasmic Reticulum in Health and Disease

2021 ◽  
Author(s):  
Vitalii Kryvenko ◽  
Olga Vagin ◽  
Laura A. Dada ◽  
Jacob I. Sznajder ◽  
István Vadász
Keyword(s):  
Endoplasmic Reticulum ◽  
Intracellular Signaling ◽  
Loss Of Function ◽  
Α Subunit ◽  
Rate Limiting Step ◽  
Atpase Subunits ◽  
A Cell ◽  
Health And Disease ◽  
And Function ◽  
Rate Limiting

Abstract The Na,K-ATPase establishes the electrochemical gradient of cells by driving an active exchange of Na+ and K+ ions while consuming ATP. The minimal functional transporter consists of a catalytic α-subunit and a β-subunit with chaperon activity. The Na,K-ATPase also functions as a cell adhesion molecule and participates in various intracellular signaling pathways. The maturation and trafficking of the Na,K-ATPase include co- and post-translational processing of the enzyme in the endoplasmic reticulum (ER) and the Golgi apparatus and subsequent delivery to the plasma membrane (PM). The ER folding of the enzyme is considered as the rate-limiting step in the membrane delivery of the protein. It has been demonstrated that only assembled Na,K-ATPase α:β-complexes may exit the organelle, whereas unassembled, misfolded or unfolded subunits are retained in the ER and are subsequently degraded. Loss of function of the Na,K-ATPase has been associated with lung, heart, kidney and neurological disorders. Recently, it has been shown that ER dysfunction, in particular, alterations in the homeostasis of the organelle, as well as impaired ER-resident chaperone activity may impede folding of Na,K-ATPase subunits, thus decreasing the abundance and function of the enzyme at the PM. Here, we summarize our current understanding on maturation and subsequent processing of the Na,K-ATPase in the ER under physiological and pathophysiological conditions. Graphic Abstract

scholarly journals Detecting long-range interactions between migrating cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
C. Metzner ◽  
F. Hörsch ◽  
C. Mark ◽  
T. Czerwinski ◽  
A. Winterl ◽  
...  
Keyword(s):  
Nk Cells ◽  
Tumor Cells ◽  
Long Range ◽  
Cooperative Behavior ◽  
Simulated Data ◽  
Movement Direction ◽  
Repulsive Interaction ◽  
Collagen Gels ◽  
Long Range Interactions ◽  
A Cell

AbstractChemotaxis enables cells to systematically approach distant targets that emit a diffusible guiding substance. However, the visual observation of an encounter between a cell and a target does not necessarily indicate the presence of a chemotactic approach mechanism, as even a blindly migrating cell can come across a target by chance. To distinguish between the chemotactic approach and blind migration, we present an objective method that is based on the analysis of time-lapse recorded cell migration trajectories: For each movement step of a cell relative to the position of a potential target, we compute a p value that quantifies the likelihood of the movement direction under the null-hypothesis of blind migration. The resulting distribution of p values, pooled over all recorded cell trajectories, is then compared to an ensemble of reference distributions in which the positions of targets are randomized. First, we validate our method with simulated data, demonstrating that it reliably detects the presence or absence of remote cell-cell interactions. In a second step, we apply the method to data from three-dimensional collagen gels, interspersed with highly migratory natural killer (NK) cells that were derived from two different human donors. We find for one of the donors an attractive interaction between the NK cells, pointing to a cooperative behavior of these immune cells. When adding nearly stationary K562 tumor cells to the system, we find a repulsive interaction between K562 and NK cells for one of the donors. By contrast, we find attractive interactions between NK cells and an IL-15-secreting variant of K562 tumor cells. We therefore speculate that NK cells find wild-type tumor cells only by chance, but are programmed to leave a target quickly after a close encounter. We provide a freely available Python implementation of our p value method that can serve as a general tool for detecting long-range interactions in collective systems of self-driven agents.

scholarly journals Redefining interferon-producing killer dendritic cells as a novel intermediate in NK-cell differentiation

Blood ◽  
2012 ◽  
Vol 119 (19) ◽  
pp. 4349-4357 ◽  
Author(s):  
Fanny Guimont-Desrochers ◽  
Geneviève Boucher ◽  
Zhongjun Dong ◽  
Martine Dupuis ◽  
André Veillette ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Nk Cells ◽  
Adoptive Transfer ◽  
Nk Cell ◽  
Cell Lineage ◽  
Current View ◽  
Antitumoral Activity ◽  
Nk Cell Differentiation ◽  
A Cell

Abstract The cell lineage origin of IFN-producing killer dendritic cells (IKDCs), which exhibit prominent antitumoral activity, has been subject to debate. Although IKDCs were first described as a cell type exhibiting both plasmacytoid DC and natural killer (NK) cell properties, the current view reflects that IKDCs merely represent activated NK cells expressing B220, which were thus renamed B220+ NK cells. Herein, we further investigate the lineage relation of B220+ NK cells with regard to other NK-cell subsets. We surprisingly find that, after adoptive transfer, B220− NK cells did not acquire B220 expression, even in the presence of potent activating stimuli. These findings strongly argue against the concept that B220+ NK cells are activated NK cells. Moreover, we unequivocally show that B220+ NK cells are highly proliferative and differentiate into mature NK cells after in vivo adoptive transfer. Additional phenotypic, functional, and transcriptional characterizations further define B220+ NK cells as immediate precursors to mature NK cells. The characterization of these novel attributes to B220+ NK cells will guide the identification of their ortholog in humans, contributing to the design of potent cancer immunotherapies.

scholarly journals Melatonin: A Novel Indolamine in Oral Health and Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
V. K. Chava ◽  
K. Sirisha
Keyword(s):  
Gastrointestinal Tract ◽  
Oral Health ◽  
Oral Cavity ◽  
Salivary Glands ◽  
In Vivo Studies ◽  
Systemic Level ◽  
A Cell ◽  
Health And Disease ◽  
Anti Oxidant

This paper attempts to summarise the findings accumulated within the last few years concerning the hormone of darkness “melatonin.” Based on its origin, from the pineal gland until recently it was portrayed exclusively as a hormone. Due to its lipophilic nature, it is accessible to every cell. Thus, in the classic sense it is a cell protector rather than a hormone. Recent studies, by Claustrat et al. (2005), detected few extrapineal sources of melatonin like retina, gastrointestinal tract, and salivary glands. Due to these sources, research by Cutando et al. (2007), is trying to explore the implications of melatonin in the oral cavity, in addition to its physiologic anti-oxidant, immunomodulatory and oncostatic functions at systemic level that may be receptor dependent or independent. Recently, certain in vivo studies by Shimozuma et al. (2011), detected the secretion of melatonin from salivary glands further emphasising its local activity. Thus, within our confines the effects of melatonin in the mouth are reviewed, adding a note on therapeutic potentials of melatonin both systemically and orally.

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