Anton T. J. Tool
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View article: Dynamics of neutrophil phenotype and function in sickle cell disease
Dynamics of neutrophil phenotype and function in sickle cell disease Open
Introduction While sickle cell disease (SCD) is primarily acknowledged as an erythrocyte disorder, emerging evidence suggests a role for altered neutrophil phenotype and function in SCD pathophysiology and disease severity. Given the confl…
View article: Platelet proteomic profiling in sitosterolemia suggests thrombocytopenia is driven by lipid disorder and not platelet aberrations
Platelet proteomic profiling in sitosterolemia suggests thrombocytopenia is driven by lipid disorder and not platelet aberrations Open
Sitosterolemia is a rare autosomal recessive genetic disorder in which patients develop hypercholesterolemia and may exhibit abnormal hematologic and/or liver test results. In this disease, dysfunction of either ABCG5 or ABCG8 results in t…
View article: Reduced myeloid commitment and increased uptake by macrophages of stem cell–derived HPS2 neutrophils
Reduced myeloid commitment and increased uptake by macrophages of stem cell–derived HPS2 neutrophils Open
Hermansky–Pudlak syndrome type 2 (HPS2) is a rare autosomal recessive disorder, caused by mutations in the AP3B1 gene, encoding the β3A subunit of the adapter protein complex 3. This results in mis-sorting of proteins within the cell. A cl…
View article: <b> Development of an Affinity-Based Probe to Profile Endogenous Human Adenosine A <sub>3</sub> Receptor Expression </b>
<b> Development of an Affinity-Based Probe to Profile Endogenous Human Adenosine A <sub>3</sub> Receptor Expression </b> Open
The adenosine A3 receptor (A3AR) is a G protein-coupled receptor (GPCR) that exerts immunomodulatory effects in pathophysiological conditions such as inflammation and cancer. Thus far, studies toward the downstream ef…
View article: Lack of eosinophil extracellular trap formation due to failure of plasma membrane breakdown in the absence of elastase
Lack of eosinophil extracellular trap formation due to failure of plasma membrane breakdown in the absence of elastase Open
Activated eosinophils are described to release eosinophil extracellular traps (EETs), which consist of the cell’s DNA covered with granule-derived antimicrobial peptides. Upon stimulation of eosinophils with the known EET-inducers phorbol …
View article: Development of an Affinity-Based Probe to profile endogenous Human Adenosine A3 Receptor Expression
Development of an Affinity-Based Probe to profile endogenous Human Adenosine A3 Receptor Expression Open
The adenosine A3 receptor (A3AR) is a G protein-coupled receptor (GPCR) that exerts immunomodulatory effects in pathophysiological conditions such as inflammation and cancer. Thus far, studies towards the downstream effects of A3AR activat…
View article: Cancer cells resist antibody-mediated destruction by neutrophils through activation of the exocyst complex
Cancer cells resist antibody-mediated destruction by neutrophils through activation of the exocyst complex Open
Background Neutrophils kill antibody-opsonized tumor cells using trogocytosis, a unique mechanism of destruction of the target plasma. This previously unknown cytotoxic process of neutrophils is dependent on antibody opsonization, Fcγ rece…
View article: Formation of neutrophil extracellular traps requires actin cytoskeleton rearrangements
Formation of neutrophil extracellular traps requires actin cytoskeleton rearrangements Open
Neutrophils are important effector cells in the host defense against invading microorganisms. One of the mechanisms they use to eliminate pathogens is the release of neutrophil extracellular traps (NETs). Although NET release and subsequen…
View article: S100A8/A9 Is a Marker for the Release of Neutrophil Extracellular Traps and Induces Neutrophil Activation
S100A8/A9 Is a Marker for the Release of Neutrophil Extracellular Traps and Induces Neutrophil Activation Open
Neutrophils are the most abundant innate immune cells in the circulation and they are the first cells recruited to sites of infection or inflammation. Almost half of the intracellular protein content in neutrophils consists of S100A8 and S…
View article: Sodium stibogluconate and CD47-SIRPα blockade overcome resistance of anti-CD20–opsonized B cells to neutrophil killing
Sodium stibogluconate and CD47-SIRPα blockade overcome resistance of anti-CD20–opsonized B cells to neutrophil killing Open
Anti-CD20 antibodies such as rituximab are broadly used to treat B-cell malignancies. These antibodies can induce various effector functions, including immune cell-mediated antibody-dependent cellular cytotoxicity (ADCC). Neutrophils can i…
View article: Myeloid Ezh2 Deficiency Limits Atherosclerosis Development
Myeloid Ezh2 Deficiency Limits Atherosclerosis Development Open
Macrophages define a key component of immune cells present in atherosclerotic lesions and are central regulators of the disease. Since epigenetic processes are important in controlling macrophage function, interfering with epigenetic pathw…
View article: Neutrophil specific granule and NETosis defects in gray platelet syndrome
Neutrophil specific granule and NETosis defects in gray platelet syndrome Open
Gray platelet syndrome (GPS) is an autosomal recessive bleeding disorder characterized by a lack of α-granules in platelets and progressive myelofibrosis. Rare loss-of-function variants in neurobeachin-like 2 (NBEAL2), a member of the fami…
View article: Kindlin3-Dependent CD11b/CD18-Integrin Activation Is Required for Potentiation of Neutrophil Cytotoxicity by CD47–SIRPα Checkpoint Disruption
Kindlin3-Dependent CD11b/CD18-Integrin Activation Is Required for Potentiation of Neutrophil Cytotoxicity by CD47–SIRPα Checkpoint Disruption Open
The CD47–signal regulatory protein-alpha (SIRPα) immune checkpoint constitutes a therapeutic target in cancer, and initial clinical studies using inhibitors of CD47–SIRPα interactions in combination with tumor-targeting antibodies show pro…
View article: Defective neutrophil development and specific granule deficiency caused by a homozygous splice-site mutation in SMARCD2
Defective neutrophil development and specific granule deficiency caused by a homozygous splice-site mutation in SMARCD2 Open
View article: Loss‐of‐function mutations in <i>CSF3R</i> cause moderate neutropenia with fully mature neutrophils: two novel pedigrees
Loss‐of‐function mutations in <i>CSF3R</i> cause moderate neutropenia with fully mature neutrophils: two novel pedigrees Open
To the Editor: The growth factor granulocyte colony-stimulating factor (G-CSF) has been described as a key regulator of neutrophil development by inducing proliferation, differentiation, and survival of myeloid progenitors. In case of infe…
View article: MKL1 deficiency results in a severe neutrophil motility defect due to impaired actin polymerization
MKL1 deficiency results in a severe neutrophil motility defect due to impaired actin polymerization Open
Megakaryoblastic leukemia 1 (MKL1) promotes the regulation of essential cell processes, including actin cytoskeletal dynamics, by coactivating serum response factor. Recently, the first human with MKL1 deficiency, leading to a novel primar…
View article: SMARCD2 neutrophil chemotaxis
SMARCD2 neutrophil chemotaxis Open
Defective chemotaxis of SMARCD2-deficient patient cells assessed with TaxiScan. Travel control and patient cells stimulated with C5a (100 nM; Video 1 = travel control and 2 = patient) or fMLF (100 nM; Video 3 = travel control and 4 = patie…
View article: Red blood cell transfusion results in adhesion of neutrophils in human endotoxemia and in critically ill patients with sepsis
Red blood cell transfusion results in adhesion of neutrophils in human endotoxemia and in critically ill patients with sepsis Open
BACKGROUND Red blood cell (RBC) transfusion is associated with adverse effects, which may involve activation of the host immune response. The effect of RBC transfusion on neutrophil Reactive Oxygen Species (ROS) production and adhesion ex …
View article: Activated neutrophils exert myeloid-derived suppressor cell activity damaging T cells beyond repair
Activated neutrophils exert myeloid-derived suppressor cell activity damaging T cells beyond repair Open
Key Points Activated neutrophils can suppress T-cell proliferation in a CD11b-dependent multistep process involving ROS production and degranulation. MDSC activity results in nonapoptotic T-cell damage.
View article: Dynamic Transcriptome-Proteome Correlation Networks Reveal Human Myeloid Differentiation and Neutrophil-Specific Programming
Dynamic Transcriptome-Proteome Correlation Networks Reveal Human Myeloid Differentiation and Neutrophil-Specific Programming Open
View article: Neutrophils as Suppressors of T Cell Proliferation: Does Age Matter?
Neutrophils as Suppressors of T Cell Proliferation: Does Age Matter? Open
Whereas, neutrophils have long been considered to mainly function as efficient innate immunity killers of micro-organisms at infected sites, they are now recognized to also be involved in modulation of adaptive immune responses. Immature a…
View article: A combined immunodeficiency with severe infections, inflammation, and allergy caused by ARPC1B deficiency
A combined immunodeficiency with severe infections, inflammation, and allergy caused by ARPC1B deficiency Open
We report the natural history, clinical manifestations, genetics, and immunohematological findings in 14 patients from 11 families with ARPC1B deficiency, delineating the spectrum of the disease that appears progressive and challenging to …
View article: Dynamics of Transcription Regulation in Human Bone Marrow Myeloid Differentiation to Mature Blood Neutrophils
Dynamics of Transcription Regulation in Human Bone Marrow Myeloid Differentiation to Mature Blood Neutrophils Open
View article: Inherited p40phox deficiency differs from classic chronic granulomatous disease
Inherited p40phox deficiency differs from classic chronic granulomatous disease Open
Biallelic loss-of-function (LOF) mutations of the NCF4 gene, encoding the p40phox subunit of the phagocyte NADPH oxidase, have been described in only 1 patient. We report on 24 p40phox-deficient patients from 12 additional families in 8 co…
View article: Loss of function NFKB1 variants are the most common monogenic cause of CVID in Europeans.
Loss of function NFKB1 variants are the most common monogenic cause of CVID in Europeans. Open
View article: Epigenomic and functional dynamics of human bone marrow myeloid differentiation to mature blood neutrophils
Epigenomic and functional dynamics of human bone marrow myeloid differentiation to mature blood neutrophils Open
Summary Neutrophils are short-lived blood cells that play a critical role in host defense against infections. To better comprehend neutrophil functions and their regulation, we provide a complete epigenetic and functional overview of their…
View article: Loss-of-function nuclear factor κB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency in Europeans
Loss-of-function nuclear factor κB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency in Europeans Open
View article: Increased circulating interleukin-8 in patients with resistance to thyroid hormone receptor α
Increased circulating interleukin-8 in patients with resistance to thyroid hormone receptor α Open
Innate immune cells have recently been identified as novel thyroid hormone (TH) target cells in which intracellular TH levels appear to play an important functional role. The possible involvement of TH receptor alpha (TRα), which is the pr…
View article: The lung is a host defense niche for immediate neutrophil-mediated vascular protection
The lung is a host defense niche for immediate neutrophil-mediated vascular protection Open
Pulmonary capillaries provide a home for neutrophil surveillance to capture bloodstream bacteria.
View article: Combined immunodeficiency with severe inflammation and allergy caused by ARPC1B deficiency
Combined immunodeficiency with severe inflammation and allergy caused by ARPC1B deficiency Open