Therapeutic Targeting of Neutrophil Granulocytes in Inflammatory Liver Disease.

Abstract:

:Neutrophil granulocytes are the most numerous type of leukocyte in humans bearing an enormous, yet largely unexplored therapeutic potential. Scientists have very recently increased their efforts to study and understand these cells which contribute to various types of inflammatory diseases and cancer. The mechanisms that regulate neutrophil recruitment to inflamed tissues and neutrophil cytotoxic activities against host tissues and pathogens require more attention. The reactive oxygen species (ROS) are a popular source of cellular stress and organ injury, and are critically expressed by neutrophils. By combating pathogens using molecular combat factors such as neutrophil extracellular traps (NETs), these are immobilized and killed i.e., by ROS. NETs and ROS are essential for the immune defense, but upon excessive activation, may also harm healthy tissue. Thus, exploring new routes for modulating their migration and activation is highly desired for creating novel anti-inflammatory treatment options. Leukocyte transmigration represents a key process for inflammatory cell infiltration to injury sites. In this review, we briefly summarize the differentiation and roles of neutrophils, with a spotlight on intravital imaging. We further discuss the potential of nanomedicines, i.e., selectin mimetics to target cell migration and influence liver disease outcome in animal models. Novel perspectives further arise from formulations of the wide array of options of small non-coding RNA such as small interfering RNA (siRNA) and micro-RNA (miR) which exhibit enzymatic functions: while siRNA binds and degrades a single mRNA based on full complementarity of binding, miR can up and down-regulate multiple targets in gene transcription and translation, mediated by partial complementarity of binding. Notably, miR is known to regulate at least 60% of the protein-coding genes and thus includes a potent strategy for a large number of targets in neutrophils. Nanomedicines can combine properties of different drugs in a single formulation, i.e., combining surface functionalization with ligands and drug delivery. Inevitably, nanomedicines accumulate in other phagocytes, a fact that should be controlled for every novel formulation to restrain activation of macrophages or modifications of the immunological synapse. Controlled drug release enabled by nanotechnological delivery systems may advance the options of modulating neutrophil activation and migration.

journal_name

Front Immunol

journal_title

Frontiers in immunology

authors

Bartneck M,Wang J

doi

10.3389/fimmu.2019.02257

subject

Has Abstract

pub_date

2019-09-20 00:00:00

pages

2257

issn

1664-3224

journal_volume

10

pub_type

杂志文章,评审
  • iRAGu: A Novel Inducible and Reversible Mouse Model for Ubiquitous Recombinase Activity.

    abstract::Developing lymphocytes express the recombination activating genes (RAGs) 1 and 2 products that form a site specific recombinase complex (RAG), introducing double strand DNA breaks (DSBs) at recombination signal sequences (RSSs) flanking the V, D, and J gene segments in the antigen receptor loci. The subsequent steps i...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01525

    authors: Bonnet M,Sarmento LM,Martins AC,Sobral D,Silva J,Demengeot J

    更新日期:2017-11-10 00:00:00

  • Del-1, an Endogenous Inhibitor of TGF-β Activation, Attenuates Fibrosis.

    abstract::Uncontrolled activation of transforming growth factor (TGF)-β results in a wide range of pathologic conditions. Therapeutic interventions to regulate TGF-β signaling during fibrosis have been developed but the effectiveness is still limited. Here, we show that developmental endothelial locus-1 (Del-1) ameliorates fibr...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.00068

    authors: Kim DY,Lee SH,Fu Y,Jing F,Kim WY,Hong SB,Song JA,Choe H,Ryu HJ,Kim M,Lim D,Kim MS,Yun CO,Lee T,Hyun H,Choi EY

    更新日期:2020-02-07 00:00:00

  • Case Report: Extensive Phosphorylation of Interleukin-1 Receptor-Associated Kinase 4 in a Patient With Schnitzler Syndrome.

    abstract::Schnitzler syndrome (SchS) is a rare autoinflammatory disease, characterized by urticarial rash, recurrent fever, osteo-articular pain/arthritis with bone condensation, and monoclonal gammopathy. Diagnosis may be difficult due to overlapping signs with other diseases. Here, we describe the case of a 62-year-old man wi...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.576200

    authors: Hodl I,Bosch P,Dreo B,Stradner MH

    更新日期:2020-09-30 00:00:00

  • A Unique Cellular and Molecular Microenvironment Is Present in Tertiary Lymphoid Organs of Patients with Spontaneous Prostate Cancer Regression.

    abstract:OBJECTIVE:Multiple solid cancers contain tertiary lymphoid organs (TLO). However, it is unclear whether they promote tumor rejection, facilitate tumor evasion, or simply whether they are a byproduct of chronic inflammation. We hypothesize that although chronic inflammation induces TLO formation, the tumor milieu can mo...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.00563

    authors: García-Hernández ML,Uribe-Uribe NO,Espinosa-González R,Kast WM,Khader SA,Rangel-Moreno J

    更新日期:2017-05-17 00:00:00

  • Negative Effect of Age, but Not of Latent Cytomegalovirus Infection on the Antibody Response to a Novel Influenza Vaccine Strain in Healthy Adults.

    abstract::Older adults are more vulnerable to influenza virus infection and at higher risk for severe complications and influenza-related death compared to younger adults. Unfortunately, influenza vaccine responses tend to be impaired in older adults due to aging of the immune system (immunosenescence). Latent infection with cy...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.00082

    authors: van den Berg SPH,Wong A,Hendriks M,Jacobi RHJ,van Baarle D,van Beek J

    更新日期:2018-01-29 00:00:00

  • Tailoring Immune Responses toward Autoimmunity: Transcriptional Regulators That Drive the Creation and Collusion of Autoreactive Lymphocytes.

    abstract::T-dependent humoral immune responses to infection involve a collaboration between B and CD4 T cell activation, migration, and co-stimulation, thereby culminating in the formation of germinal centers (GCs) and eventual differentiation into memory cells and long-lived plasma cells (PCs). CD4 T cell-derived signals drive...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.00482

    authors: Good-Jacobson KL,Groom JR

    更新日期:2018-03-08 00:00:00

  • Granulomas and Inflammation: Host-Directed Therapies for Tuberculosis.

    abstract::Tuberculosis (TB) remains a leading global health problem that is aggravated by emergence of drug-resistant strains, which account for increasing number of treatment-refractory cases. Thus, eradication of this disease will strongly require better therapeutic strategies. Identification of host factors promoting disease...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2016.00434

    authors: Ndlovu H,Marakalala MJ

    更新日期:2016-10-24 00:00:00

  • Multilayer Control of B Cell Activation by the B Cell Antigen Receptor: Following Themes Initiated With Bill Paul.

    abstract::This article describes the work I did in Bill Paul's lab as a postdoctoral fellow between 1979 and 1983, and to a lesser extent puts that work in the context of other work on B cell activation and antibody responses that was going on in Bill's lab at that time and shortly beforehand, including the discovery of interle...

    journal_title:Frontiers in immunology

    pub_type: 传,历史文章,杂志文章

    doi:10.3389/fimmu.2018.00739

    authors: DeFranco AL

    更新日期:2018-04-23 00:00:00

  • Selective Manipulation of the Gut Microbiota Improves Immune Status in Vertebrates.

    abstract::All animals develop in association with complex microbial communities. It is now well established that commensal microbiota is essential for the correct functionality of each organ in the host. Particularly, the commensal gastro-intestinal microbiota (CGIM) is a key factor for development, immunity and nutrient conver...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2015.00512

    authors: Montalban-Arques A,De Schryver P,Bossier P,Gorkiewicz G,Mulero V,Gatlin DM 3rd,Galindo-Villegas J

    更新日期:2015-10-09 00:00:00

  • PI3Kδ Inhibition Enhances the Antitumor Fitness of Adoptively Transferred CD8+ T Cells.

    abstract::Phosphatidylinositol-3-kinase p110δ (PI3Kδ) inhibition by Idelalisib (CAL-101) in hematological malignancies directly induces apoptosis in cancer cells and disrupts immunological tolerance by depleting regulatory T cells. Yet, little is known about the direct impact of PI3Kδ blockade on effector T cells from CAL-101 t...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01221

    authors: Bowers JS,Majchrzak K,Nelson MH,Aksoy BA,Wyatt MM,Smith AS,Bailey SR,Neal LR,Hammerbacher JE,Paulos CM

    更新日期:2017-09-29 00:00:00

  • CD28 Individual Signaling Up-regulates Human IL-17A Expression by Promoting the Recruitment of RelA/NF-κB and STAT3 Transcription Factors on the Proximal Promoter.

    abstract::CD28 is an important co-stimulatory receptor for T lymphocytes that, in humans, delivers TCR-independent signal leading to the up-regulation of pro-inflammatory cytokines. We have recently reported that CD28 autonomous signaling induces the expression of IL-17A in peripheral CD4+ T lymphocytes from healthy donors, mul...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.00864

    authors: Kunkl M,Mastrogiovanni M,Porciello N,Caristi S,Monteleone E,Arcieri S,Tuosto L

    更新日期:2019-04-24 00:00:00

  • Pulmonary Exposure to Magnéli Phase Titanium Suboxides Results in Significant Macrophage Abnormalities and Decreased Lung Function.

    abstract::Coal is one of the most abundant and economic sources for global energy production. However, the burning of coal is widely recognized as a significant contributor to atmospheric particulate matter linked to deleterious respiratory impacts. Recently, we have discovered that burning coal generates large quantities of ot...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.02714

    authors: McDaniel DK,Ringel-Scaia VM,Morrison HA,Coutermarsh-Ott S,Council-Troche M,Angle JW,Perry JB,Davis G,Leng W,Minarchick V,Yang Y,Chen B,Reece SW,Brown DA,Cecere TE,Brown JM,Gowdy KM,Hochella MF Jr,Allen IC

    更新日期:2019-11-28 00:00:00

  • Imaging the Bone-Immune Cell Interaction in Bone Destruction.

    abstract::Bone is a highly dynamic organ that is continuously being remodeled by the reciprocal interactions between bone and immune cells. We have originally established an advanced imaging system for visualizing the in vivo behavior of osteoclasts and their precursors in the bone marrow cavity using two-photon microscopy. Usi...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.00596

    authors: Hasegawa T,Kikuta J,Ishii M

    更新日期:2019-03-26 00:00:00

  • Immune Tolerance Maintained by Cooperative Interactions between T Cells and Antigen Presenting Cells Shapes a Diverse TCR Repertoire.

    abstract::The T cell population in an individual needs to avoid harmful activation by self peptides while maintaining the ability to respond to an unknown set of foreign peptides. This property is acquired by a combination of thymic and extra-thymic mechanisms. We extend current models for the development of self/non-self discr...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2015.00360

    authors: Best K,Chain B,Watkins C

    更新日期:2015-08-07 00:00:00

  • Maternal Immune Activation Alters Fetal Brain Development and Enhances Proliferation of Neural Precursor Cells in Rats.

    abstract::Maternal immune activation (MIA) caused by exposure to pathogens or inflammation during critical periods of neurodevelopment is a major risk factor for behavioral deficits and psychiatric illness in offspring. A spectrum of behavioral abnormalities can be recapitulated in rodents by inducing MIA using the viral mimeti...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.01145

    authors: Baines KJ,Hillier DM,Haddad FL,Rajakumar N,Schmid S,Renaud SJ

    更新日期:2020-06-09 00:00:00

  • Microglia and Inflammatory Responses in Diabetic Retinopathy.

    abstract::Diabetic retinopathy is a vision-threatening disease affecting neurons and microvasculature of the retina. The development of this disease is associated with the action of inflammatory factors that are connected to the activation of microglial cells, the resident tissue macrophages of the CNS. In the quiescent state, ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2020.564077

    authors: Kinuthia UM,Wolf A,Langmann T

    更新日期:2020-11-06 00:00:00

  • Structure Based Refinement of a Humanized Monoclonal Antibody That Targets Tumor Antigen Disialoganglioside GD2.

    abstract::Disialoganglioside GD2 is an important target on several pediatric and adult cancer types including neuroblastoma, retinoblastoma, melanoma, small-cell lung cancer, brain tumors, sarcomas, and cancer stem cells. We have utilized structural and computational methods to refine the framework of humanized monoclonal antib...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2014.00372

    authors: Ahmed M,Hu J,Cheung NK

    更新日期:2014-08-14 00:00:00

  • IgA and FcαRI: Pathological Roles and Therapeutic Opportunities.

    abstract::Immunoglobulin A (IgA) is the most abundant antibody class present at mucosal surfaces. The production of IgA exceeds the production of all other antibodies combined, supporting its prominent role in host-pathogen defense. IgA closely interacts with the intestinal microbiota to enhance its diversity, and IgA has a pas...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.00553

    authors: Breedveld A,van Egmond M

    更新日期:2019-03-22 00:00:00

  • Role of Macrophage Migration Inhibitory Factor in Obesity, Insulin Resistance, Type 2 Diabetes, and Associated Hepatic Co-Morbidities: A Comprehensive Review of Human and Rodent Studies.

    abstract::Obesity is associated with a chronic low-grade inflammatory state that drives the -development of obesity-related co-morbidities such as insulin resistance/type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease. This metabolic inflammation is thought to originate in the adipose tissue, ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2015.00308

    authors: Morrison MC,Kleemann R

    更新日期:2015-06-15 00:00:00

  • Directed Differentiation of Human Induced Pluripotent Stem Cells into Dendritic Cells Displaying Tolerogenic Properties and Resembling the CD141+ Subset.

    abstract::The advent of induced pluripotent stem cells (iPSCs) has begun to revolutionize cell therapy by providing a convenient source of rare cell types not normally available from patients in sufficient numbers for therapeutic purposes. In particular, the development of protocols for the differentiation of populations of leu...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01935

    authors: Sachamitr P,Leishman AJ,Davies TJ,Fairchild PJ

    更新日期:2018-01-08 00:00:00

  • Role of Epstein-Barr Virus in Pathogenesis and Racial Distribution of IgA Nephropathy.

    abstract::IgA nephropathy (IgAN) is the dominant type of primary glomerulonephritis worldwide. However, IgAN rarely affects African Blacks and is uncommon in African Americans. Polymeric IgA1 with galactose-deficient hinge-region glycans is recognized as auto-antigen by glycan-specific antibodies, leading to formation of circul...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.00267

    authors: Zachova K,Kosztyu P,Zadrazil J,Matousovic K,Vondrak K,Hubacek P,Julian BA,Moldoveanu Z,Novak Z,Kostovcikova K,Raska M,Mestecky J

    更新日期:2020-02-28 00:00:00

  • Neutrophil Extracellular Traps and Its Implications in Inflammation: An Overview.

    abstract::In addition to physical barriers, neutrophils are considered a part of the first line of immune defense. They can be found in the bloodstream, with a lifespan of 6-8 h, and in tissue, where they can last up to 7 days. The mechanisms that neutrophils utilize for host defense are phagocytosis, degranulation, cytokine pr...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2017.00081

    authors: Delgado-Rizo V,Martínez-Guzmán MA,Iñiguez-Gutierrez L,García-Orozco A,Alvarado-Navarro A,Fafutis-Morris M

    更新日期:2017-02-06 00:00:00

  • Nanobodies and Nanobody-Based Human Heavy Chain Antibodies As Antitumor Therapeutics.

    abstract::Monoclonal antibodies have revolutionized cancer therapy. However, delivery to tumor cells in vivo is hampered by the large size (150 kDa) of conventional antibodies. The minimal target recognition module of a conventional antibody is composed of two non-covalently associated variable domains (VH and VL). The proper o...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2017.01603

    authors: Bannas P,Hambach J,Koch-Nolte F

    更新日期:2017-11-22 00:00:00

  • Novel, Anti-hTNF-α Variable New Antigen Receptor Formats with Enhanced Neutralizing Potency and Multifunctionality, Generated for Therapeutic Development.

    abstract::The management of chronic inflammatory diseases, such as inflammatory bowel disease, psoriasis, and rheumatoid arthritis has significantly improved over the last decade with the clinical availability of anti-TNF-α biologics. Despite this undoubted treatment success, a combination of acquired resistance together with a...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01780

    authors: Ubah OC,Steven J,Kovaleva M,Ferguson L,Barelle C,Porter AJR,Barelle CJ

    更新日期:2017-12-22 00:00:00

  • Indole Treatment Alleviates Intestinal Tissue Damage Induced by Chicken Coccidiosis Through Activation of the Aryl Hydrocarbon Receptor.

    abstract::Indoles, as the ligands of aryl hydrocarbon receptor (AhR), have been shown to possess immune-modulating property in terms of the balancing between regulatory T cells (Treg) and T helper 17 cells (Th17) activities. In the present study, we examined the effects of dietary indoles, 3,3'-diindolylmethane (DIM) and indole...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.00560

    authors: Kim WH,Lillehoj HS,Min W

    更新日期:2019-03-26 00:00:00

  • Emerging Concepts about NAIP/NLRC4 Inflammasomes.

    abstract::Neuronal apoptosis inhibitory protein (NAIP)/NOD-like receptor (NLR) containing a caspase activating and recruitment domain (CARD) 4 (NLRC4) inflammasome complexes are activated in response to proteins from virulent bacteria that reach the cell cytosol. Specific NAIP proteins bind to the agonists and then physically a...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2014.00309

    authors: Lage SL,Longo C,Branco LM,da Costa TB,Buzzo Cde L,Bortoluci KR

    更新日期:2014-07-02 00:00:00

  • IL-34 Actions on FOXP3+ Tregs and CD14+ Monocytes Control Human Graft Rejection.

    abstract::Cytokines are major players regulating immune responses toward inflammatory and tolerogenic results. In organ and bone marrow transplantation, new reagents are needed to inhibit tissue destructive mechanisms and eventually induce immune tolerance without overall immunosuppression. IL-34 is a cytokine with no significa...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.01496

    authors: Bézie S,Freuchet A,Sérazin C,Salama A,Vimond N,Anegon I,Guillonneau C

    更新日期:2020-08-11 00:00:00

  • Predictable Irreversible Switching Between Acute and Chronic Inflammation.

    abstract::Many a disease associates with inflammation. Upon binding of antigen-antibody complexes to immunoglobulin-like receptors, mast cells release tumor necrosis factor-α and proteases, causing fibroblasts to release endogenous antigens that may be cross reactive with exogenous antigens. We made a predictive dynamic map of ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.01596

    authors: Abudukelimu A,Barberis M,Redegeld FA,Sahin N,Westerhoff HV

    更新日期:2018-08-07 00:00:00

  • Autophagy and Autophagy-Related Proteins in CNS Autoimmunity.

    abstract::Autophagy comprises a heterogeneous group of cellular pathways that enables eukaryotic cells to deliver cytoplasmic constituents for lysosomal degradation, to recycle nutrients, and to survive during starvation. In addition to these primordial functions, autophagy has emerged as a key mechanism in orchestrating innate...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2017.00165

    authors: Keller CW,Lünemann JD

    更新日期:2017-02-27 00:00:00

  • Piperlongumine Acts as an Immunosuppressant by Exerting Prooxidative Effects in Human T Cells Resulting in Diminished TH17 but Enhanced Treg Differentiation.

    abstract::Piperlongumine (PL), a natural small molecule derived from the Piper longum Linn plant, has received growing interest as a prooxidative drug with promising anticancer properties. Yet, the influence of PL on primary human T cells remained elusive. Knowledge of this is of crucial importance, however, since T cells in pa...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.01172

    authors: Liang J,Ziegler JD,Jahraus B,Orlik C,Blatnik R,Blank N,Niesler B,Wabnitz G,Ruppert T,Hübner K,Balta E,Samstag Y

    更新日期:2020-06-12 00:00:00