Nonfunctional TGF-β/ALK1/ENG signaling pathway supports neutrophil proangiogenic activity in hereditary hemorrhagic telangiectasia.

The transforming growth factor β (TGF-β)/ALK1/ENG signaling pathway maintains quiescent state of endothelial cells, but at the same time, it regulates neutrophil functions. Importantly, mutations of this pathway lead to a rare autosomal disorder called hereditary hemorrhagic telangiectasia (HHT), characterized with abnormal blood vessel formation (angiogenesis). As neutrophils are potent regulators of angiogenesis, we investigated how disturbed TGF-β/ALK1/ENG signaling influences angiogenic properties of these cells in HHT.

TLR2-induced CD8 T-cell deactivation shapes dendritic cell differentiation in the bone marrow during sepsis.

Sepsis is associated with profound immune dysregulation that increases the risk for life-threatening secondary infections: Dendritic cells (DCs) undergo functional reprogramming due to yet unknown changes during differentiation in the bone marrow (BM). In parallel, lymphopenia and exhaustion of T lymphocytes interfere with antigen-specific adaptive immunity. We hypothesized that there exists a link between T cells and the modulation of DC differentiation in the BM during murine polymicrobial sepsis.

During early stages of cancer, neutrophils initiate anti-tumor immune responses in tumor-draining lymph nodes.

Tumor-draining lymph nodes (LNs) play a crucial role during cancer spread and in initiation of anti-cancer adaptive immunity. Neutrophils form a substantial population of cells in LNs with poorly understood functions. Here, we demonstrate that, during head and neck cancer (HNC) progression, tumor-associated neutrophils transmigrate to LNs and shape anti-tumor responses in a stage-dependent manner.

IFNAR1 Deficiency Impairs Immunostimulatory Properties of Neutrophils in Tumor-Draining Lymph Nodes.

Tumor-draining lymph nodes (TDLNs) are the first organs where the metastatic spread of different types of cancer, including head and neck cancer (HNC), occurs and have therefore high prognostic relevance. Moreover, first anti-cancer immune responses have been shown to be initiated in such LNs tumor-educated myeloid cells. Among myeloid cells present in TDLNs, neutrophils represent a valuable population and considerably participate in the activation of effector lymphocytes there.

The Good, the Bad, and the Ugly: Neutrophils, Angiogenesis, and Cancer.

Angiogenesis, the formation of new blood vessels from already existing vasculature, is tightly regulated by pro- and anti-angiogenic stimuli and occurs under both physiological and pathological conditions. Tumor angiogenesis is central for tumor development, and an "angiogenic switch" could be initiated by multiple immune cells, such as neutrophils. Tumor-associated neutrophils promote tumor angiogenesis by the release of both conventional and non-conventional pro-angiogenic factors.

SIRT1-mediated deacetylation of FOXO3a transcription factor supports pro-angiogenic activity of interferon-deficient tumor-associated neutrophils.

Angiogenesis plays an important role during tumor growth and metastasis. We could previously show that Type I interferon (IFN)-deficient tumor-associated neutrophils (TANs) show strong pro-angiogenic activity, and stimulate tumor angiogenesis and growth. However, the exact mechanism responsible for their pro-angiogenic shift is not clear.

B-Helper Neutrophils in Regional Lymph Nodes Correlate with Improved Prognosis in Patients with Head and Neck Cancer.

The role of neutrophils during cancer formation and elimination is diverse. Here, for the first time, we investigate neutrophil helper cells (N), their influence on B cell activity in the regional lymph nodes (RLN) of head-and-neck cancer patients and the effect of this neutrophil/B cell interaction on patient prognosis. Circulating and RLN neutrophils of patients with stage I-IV head-and-neck squamous cell carcinoma were investigated with flow cytometry and qPCR.

Oral Neutrophils: Underestimated Players in Oral Cancer.

The composition of the oral milieu reflects oral health. Saliva provides an environment for multiple microorganisms, and contains soluble factors and immune cells. Neutrophils, which rapidly react on the changes in the microenvironment, are a major immune cell population in saliva and thus may serve as a biomarker for oral pathologies.

Impaired Release of Neutrophil Extracellular Traps and Anemia-Associated T Cell Deficiency in Hereditary Hemorrhagic Telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is characterized by mucocutaneous telangiectases and visceral vascular malformations. Individuals suffering from HHT have a significantly increased risk of bacterial infections, but the mechanisms involved in this are not clear. White blood cell subpopulations were estimated with flow cytometry in 79 patients with HHT and 45 healthy individuals, and association with clinicopathological status was assessed.

Neutrophil Maturation and Survival Is Controlled by IFN-Dependent Regulation of NAMPT Signaling.

Granulocyte-colony stimulating factor (G-CSF)/nicotinamide phosphoribosyltransferase (NAMPT) signaling has been shown to be crucial for the modulation of neutrophil development and functionality. As this signaling pathway is significantly suppressed by type I interferons (IFNs), we aimed to study how the regulation of neutrophil differentiation and phenotype is altered in IFN-deficient mice during granulopoiesis. The composition of bone marrow granulocyte progenitors and their expression were assessed in bone marrow of type I IFN receptor knockout ( mice and compared to wild-type animals.

Detrimental Effect of Type I IFNs During Acute Lung Infection With Is Mediated Through the Stimulation of Neutrophil NETosis.

is an opportunistic multidrug-resistant pathogen, able to grow in biofilms. It causes life-threatening complications in diseases characterized by the up-regulation of type I interferon (IFN) signaling, such as cancer or viral infections. Since type I IFNs regulate multiple functions of neutrophils, which constitute the first line of anti-bacterial host defense, in this work we aimed to study how interferon-activated neutrophils influence the course of infection of the lung.

Prognostic Role of Blood NETosis in the Progression of Head and Neck Cancer.

Neutrophil extracellular traps (NETs) represent web-like structures consisting of externalized DNA decorated with granule proteins that are responsible for trapping and killing bacteria. However, undesirable effects of NET formation during carcinogenesis, such as metastasis support, have been described. In the present study, we evaluated the correlation between NETosis and disease progression in head and neck cancer (HNC) patients in order to establish a valid biomarker for an early detection and monitoring of HNC progression.

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo.

The contribution of neutrophils to the regulation of tumorigenesis is getting increased attention. These cells are heterogeneous, and depending on the tumor milieu can possess pro- or anti-tumor capacity. One of the important cytokines regulating neutrophil functions in a tumor context are type I interferons.

NAMPT signaling is critical for the proangiogenic activity of tumor-associated neutrophils.

Tumor-associated neutrophils (TANs) regulate many processes associated with tumor progression, and depending on the microenvironment, they can exhibit pro- or antitumor functions. However, the molecular mechanisms regulating their tumorigenicity are not clear. Using transplantable tumor models, we showed here that nicotinamide phosphoribosyltransferase (NAMPT), a molecule involved in CSF3R downstream signaling, is essential for tumorigenic conversion of TANs and their pro-angiogenic switch.

The Essential Role of Type I Interferons in Differentiation and Activation of Tumor-Associated Neutrophils.

Type I interferons (IFNs) were first characterized in the process of viral interference. However, since then, IFNs are found to be involved in a wide range of biological processes. In the mouse, type I IFNs comprise a large family of cytokines.

Treg/Th17 balance in stable CAD patients with different stages of coronary atherosclerosis.

Objective. Immune processes play a significant role in atherosclerosis plaque progression. Regulatory T cells and T helpers 17 were shown to possess anti- and pro-atherogenic activity, respectively.

CD4(+)CD25(high)CD127(low) regulatory T cells in patients with stable angina and their dynamics after intracoronary sirolimus-eluting stent implantation.

Rapamycin contributes to the expansion of regulatory T cells (Tregs) in vitro. We investigated CD4(+)CD25(high)CD127(low) Treg level dynamics as well as the major parameters of cell immunity and sCD25 and highly sensitive C-reactive protein (hsCRP) concentrations in the blood of patients after coronary stenting (CS) with sirolimus (rapamycin)-eluting stents (SES; n = 43). The relation between initial Treg values and the severity of coronary atherosclerosis was observed.