scholarly journals Invadosome-Mediated Human Extracellular Matrix Degradation by Entamoeba histolytica

2018 ◽  
Vol 86 (9) ◽  
Author(s):  
Muhammad M. Hasan ◽  
Jose E. Teixeira ◽  
Christopher D. Huston
Keyword(s):  
Extracellular Matrix ◽  
Entamoeba Histolytica ◽  
Mammalian Cells ◽  
Protozoan Parasite ◽  
Human Colon ◽  
Colonic Tissue ◽  
Colon Tissue ◽  
Content Type ◽  
Tissue Invasion ◽  
And Function

ABSTRACT Entamoeba histolytica is a protozoan parasite that causes invasive amoebiasis when it invades the human colon. Tissue invasion requires a shift from an adhesive lifestyle in the colonic lumen to a motile and extracellular matrix (ECM) degradative lifestyle in the colonic tissue layers. How the parasite regulates these two lifestyles is largely unknown. Previously, we showed that silencing the E. histolytica surface metalloprotease EhMSP-1 results in parasites that are hyperadherent and less motile. To better understand the molecular mechanism of this phenotype, we now show that the parasites with EhMSP-1 silenced cannot efficiently form specialized dot-like polymerized actin (F actin) structures upon interaction with the human ECM component fibronectin. We characterized these F actin structures and found that they are very short-lived structures that are the sites of fibronectin degradation. Motile mammalian cells form F actin structures called invadosomes that are similar in stability and function to these amoebic actin dots. Therefore, we propose here that E. histolytica forms amoebic invadosomes to facilitate colonic tissue invasion.

scholarly journals Localization and Targeting of an Unusual Pyridine Nucleotide Transhydrogenase in Entamoeba histolytica

2010 ◽  
Vol 9 (6) ◽  
pp. 926-933 ◽  
Author(s):  
Mohammad Abu Yousuf ◽  
Fumika Mi-ichi ◽  
Kumiko Nakada-Tsukui ◽  
Tomoyoshi Nozaki
Keyword(s):  
Entamoeba Histolytica ◽  
Fluorescent Protein ◽  
Physiological Role ◽  
Protozoan Parasite ◽  
Pyridine Nucleotide ◽  
Immunofluorescence Assay ◽  
Chemical Degradation ◽  
Content Type ◽  
Targeting Signal ◽  
Pyridine Nucleotide Transhydrogenase

ABSTRACT Pyridine nucleotide transhydrogenase (PNT) catalyzes the direct transfer of a hydride-ion equivalent between NAD(H) and NADP(H) in bacteria and the mitochondria of eukaryotes. PNT was previously postulated to be localized to the highly divergent mitochondrion-related organelle, the mitosome, in the anaerobic/microaerophilic protozoan parasite Entamoeba histolytica based on the potential mitochondrion-targeting signal. However, our previous proteomic study of isolated phagosomes suggested that PNT is localized to organelles other than mitosomes. An immunofluorescence assay using anti-E. histolytica PNT (EhPNT) antibody raised against the NADH-binding domain showed a distribution to the membrane of numerous vesicles/vacuoles, including lysosomes and phagosomes. The domain(s) required for the trafficking of PNT to vesicles/vacuoles was examined by using amoeba transformants expressing a series of carboxyl-terminally truncated PNTs fused with green fluorescent protein or a hemagglutinin tag. All truncated PNTs failed to reach vesicles/vacuoles and were retained in the endoplasmic reticulum. These data indicate that the putative targeting signal is not sufficient for the trafficking of PNT to the vesicular/vacuolar compartments and that full-length PNT is necessary for correct transport. PNT displayed a smear of >120 kDa on SDS-PAGE gels. PNGase F and tunicamycin treatment, chemical degradation of carbohydrates, and heat treatment of PNT suggested that the apparent aberrant mobility of PNT is likely attributable to its hydrophobic nature. PNT that is compartmentalized to the acidic compartments is unprecedented in eukaryotes and may possess a unique physiological role in E. histolytica.

scholarly journals Evidence That Hyaluronidase Is Not Involved in Tissue Invasion of the Protozoan Parasite Entamoeba histolytica

2000 ◽  
Vol 68 (5) ◽  
pp. 3053-3055 ◽  
Author(s):  
Rosa Nickel ◽  
Robert Stern ◽  
Matthias Leippe
Keyword(s):  
Entamoeba Histolytica ◽  
Protozoan Parasite ◽  
Hyaluronidase Activity ◽  
Tissue Invasion

ABSTRACT As previous reports suggested that a hyaluronidase is involved in tissue invasion of Entamoeba histolytica, we searched for such an activity in trophozoite extracts. A hyaluronidase activity was not detectable in long-term cultures or in amoebae freshly passaged through a gerbil liver, as evidenced by four different techniques.

scholarly journals Knockdown of Five Genes Encoding Uncharacterized Proteins Inhibits Entamoeba histolytica Phagocytosis of Dead Host Cells

2016 ◽  
Vol 84 (4) ◽  
pp. 1045-1053 ◽  
Author(s):  
Adam Sateriale ◽  
Peter Miller ◽  
Christopher D. Huston
Keyword(s):  
Host Cell ◽  
Entamoeba Histolytica ◽  
Protozoan Parasite ◽  
Host Cells ◽  
Data Set ◽  
Feed Forward ◽  
Content Type ◽  
Genes Encoding ◽  
Relative Specificity ◽  
Cell Engulfment

Entamoeba histolyticais the protozoan parasite that causes invasive amebiasis, which is endemic to many developing countries and characterized by dysentery and liver abscesses. The virulence ofE. histolyticacorrelates with the degree of host cell engulfment, or phagocytosis, andE. histolyticaphagocytosis alters amebic gene expression in a feed-forward manner that results in an increased phagocytic ability. Here, we used a streamlined RNA interference screen to silence the expression of 15 genes whose expression was upregulated in phagocyticE. histolyticatrophozoites to determine whether these genes actually function in the phagocytic process. When five of these genes were silenced, amebic strains with significant decreases in the ability to phagocytose apoptotic host cells were produced. Phagocytosis of live host cells, however, was largely unchanged, and the defects were surprisingly specific for phagocytosis. Two of the five encoded proteins, which we namedE. histolyticaILWEQ (EhILWEQ) andE. histolyticaBAR (EhBAR), were chosen for localization via SNAP tag labeling and localized to the site of partially formed phagosomes. Therefore, both EhILWEQ and EhBAR appear to contribute toE. histolyticavirulence through their function in phagocytosis, and the large proportion (5/15 [33%]) of gene-silenced strains with a reduced ability to phagocytose host cells validates the previously published microarray data set demonstrating feed-forward control ofE. histolyticaphagocytosis. Finally, although only limited conclusions can be drawn from studies using the virulence-deficient G3Entamoebastrain, the relative specificity of the defects induced for phagocytosis of apoptotic cells but not healthy cells suggests that cell killing may play a rate-limiting role in the process ofEntamoeba histolyticahost cell engulfment.

The small GTP-binding protein RacG regulates uroid formation in the protozoan parasite Entamoeba histolytica

1998 ◽  
Vol 111 (12) ◽  
pp. 1729-1739 ◽  
Author(s):  
N. Guillen ◽  
P. Boquet ◽  
P. Sansonetti
Keyword(s):  
Cell Polarity ◽  
Entamoeba Histolytica ◽  
Mammalian Cells ◽  
Protozoan Parasite ◽  
Small Gtpases ◽  
Eukaryotic Cells ◽  
Protein Activity ◽  
Surface Receptors ◽  
Receptor Complexes ◽  
Murine Fibroblasts

Entamoeba histolytica is a protozoan parasite that invades human intestine leading to ulceration and destruction of tissue. Amoebic movement and phagocytosis of human cells is accompanied by characteristic changes in cell morphology. Amoebae become polarized, developing a frontal pseudopod and a well-defined rear zone of membrane accumulation designated the uroid. In motile eukaryotic cells, a phenomenon that contributes to movement is the capping of receptors at the cell surface. During the capping process, E. histolytica concentrates ligand-receptor complexes in the uroid. Interestingly, some of these surface receptors are involved in the survival of the parasite. While looking for regulators of capping and uroid formation, we identified RacG, an E. histolytica protein that is homologous to human Rac1. This protein belongs to the Rac subfamily of small GTPases implicated in interactions between the actin cytoskeleton and the membrane of mammalian cells. Cloning of the EhracG gene and analysis of the protein activity either in murine fibroblasts or in E. histolytica revealed that EhRacG induces a characteristic Rac phenotype. When expressed in amoebae, an EhRacG-V12 mutant protein not only deregulated cell polarity, but also caused a defect in cytokinesis. Analysis of the cytoskeleton in amoebae bearing this mutant revealed that F-actin concentrated at the periphery of the cell. In addition, the number and localization of uroids were modified. These results suggest a role for EhRacG in amoebic morphogenesis and cytokinesis.

scholarly journals Mass Spectrometric Analysis of l-Cysteine Metabolism: Physiological Role and Fate of l-Cysteine in the Enteric Protozoan Parasite Entamoeba histolytica

mBio ◽  
2014 ◽  
Vol 5 (6) ◽  
Author(s):  
Ghulam Jeelani ◽  
Dan Sato ◽  
Tomoyoshi Soga ◽  
Haruo Watanabe ◽  
Tomoyoshi Nozaki
Keyword(s):  
Oxidative Stress ◽  
Amino Acid ◽  
Carboxylic Acid ◽  
Stable Isotope ◽  
Carboxylic Acids ◽  
Entamoeba Histolytica ◽  
Protozoan Parasite ◽  
Protozoan Parasites ◽  
Metabolic Fate ◽  
Content Type

ABSTRACTl-Cysteine is essential for virtually all living organisms, from bacteria to higher eukaryotes. Besides having a role in the synthesis of virtually all proteins and of taurine, cysteamine, glutathione, and other redox-regulating proteins,l-cysteine has important functions under anaerobic/microaerophilic conditions. In anaerobic or microaerophilic protozoan parasites, such asEntamoeba histolytica,l-cysteine has been implicated in growth, attachment, survival, and protection from oxidative stress. However, a specific role of this amino acid or related metabolic intermediates is not well understood. In this study, using stable-isotope-labeledl-cysteine and capillary electrophoresis-time of flight mass spectrometry, we investigated the metabolism ofl-cysteine inE. histolytica. [U-13C3,15N]l-cysteine was rapidly metabolized into three unknown metabolites, besidesl-cystine andl-alanine. These metabolites were identified as thiazolidine-4-carboxylic acid (T4C), 2-methyl thiazolidine-4-carboxylic acid (MT4C), and 2-ethyl-thiazolidine-4-carboxylic acid (ET4C), the condensation products ofl-cysteine with aldehydes. We demonstrated that these 2-(R)-thiazolidine-4-carboxylic acids serve for storage ofl-cysteine. Liberation ofl-cysteine occurred when T4C was incubated with amebic lysates, suggesting enzymatic degradation of thesel-cysteine derivatives. Furthermore, T4C and MT4C significantly enhanced trophozoite growth and reduced intracellular reactive oxygen species (ROS) levels when it was added to cultures, suggesting that 2-(R)-thiazolidine-4-carboxylic acids are involved in the defense against oxidative stress.IMPORTANCEAmebiasis is a human parasitic disease caused by the protozoan parasiteEntamoeba histolytica. In this parasite,l-cysteine is the principal low-molecular-weight thiol and is assumed to play a significant role in supplying the amino acid during trophozoite invasion, particularly when the parasites move from the anaerobic intestinal lumen to highly oxygenated tissues in the intestine and the liver. It is well known thatE. histolyticaneeds a comparatively high concentration ofl-cysteine for its axenic cultivation. However, the reason for and the metabolic fate ofl-cysteine in this parasite are not well understood. Here, using a metabolomic and stable-isotope-labeled approach, we investigated the metabolic fate of this amino acid in these parasites. We found thatl-cysteine inside the cell rapidly reacts with aldehydes to form 2-(R)-thiazolidine-4-carboxylic acid. We showed that these 2-(R)-thiazolidine-4-carboxylic derivatives serve as anl-cysteine source, promote growth, and protect cells against oxidative stress by scavenging aldehydes and reducing the ROS level. Our findings represent the first demonstration of 2-(R)-thiazolidine-4-carboxylic acids and their roles in protozoan parasites.

The extracellular matrix of the central and peripheral nervous systems: structure and function

1988 ◽  
Vol 69 (2) ◽  
pp. 155-170 ◽  
Author(s):  
James T. Rutka ◽  
Gerard Apodaca ◽  
Robert Stern ◽  
Mark Rosenblum
Keyword(s):  
Extracellular Matrix ◽  
Nervous System ◽  
Cell Types ◽  
Structure And Function ◽  
Nervous Systems ◽  
Content Type ◽  
Body Of Knowledge ◽  
Central Nervous Systems ◽  
Biological Adhesive ◽  
And Function

✓ The extracellular matrix (ECM) is the naturally occurring substrate upon which cells migrate, proliferate, and differentiate. The ECM functions as a biological adhesive that maintains the normal cytoarchitecture of different tissues and defines the key spatial relationships among dissimilar cell types. A loss of coordination and an alteration in the interactions between mesenchymal cells and epithelial cells separated by an ECM are thought to be fundamental steps in the development and progression of cancer. Although a substantial body of knowledge has been accumulated concerning the role of the ECM in most other tissues, much less is known of the structure and function of the ECM in the nervous system. Recent experiments in mammalian systems have shown that an increased knowledge of the ECM in the nervous system can lead to a better understanding of complex neurobiological processes under developmental, normal, and pathological conditions. This review focuses on the structure and function of the ECM in the peripheral and central nervous systems and on the importance of ECM macromolecules in axonal regeneration, cerebral edema, and cerebral neoplasia.

scholarly journals The Golgin Protein RUD3 Regulates Fusarium graminearum Growth and Virulence

2021 ◽  
Vol 87 (6) ◽  
Author(s):  
Chenyu Wang ◽  
Yao Wang ◽  
Liyuan Zhang ◽  
Ziyi Yin ◽  
Yuancun Liang ◽  
...  
Keyword(s):  
Fusarium Graminearum ◽  
Vegetative Growth ◽  
Mammalian Cells ◽  
Cellular Localization ◽  
Pathogenic Fungus ◽  
Coiled Coil ◽  
Effective Control ◽  
Content Type ◽  
Ascospore Discharge ◽  
And Function

ABSTRACT Golgins are coiled-coil proteins that play prominent roles in maintaining the structure and function of the Golgi complex. However, the role of golgin proteins in phytopathogenic fungi remains poorly understood. In this study, we functionally characterized the Fusarium graminearum golgin protein RUD3, a homolog of ScRUD3/GMAP-210 in Saccharomyces cerevisiae and mammalian cells. Cellular localization observation revealed that RUD3 is located in the cis-Golgi. Deletion of RUD3 caused defects in vegetative growth, ascospore discharge, deoxynivalenol (DON) production, and virulence. Moreover, the Δrud3 mutant showed reduced expression of tri genes and impairment of the formation of toxisomes, both of which play essential roles in DON biosynthesis. We further used green fluorescent protein (GFP)-tagged SNARE protein SEC22 (SEC22-GFP) as a tool to study the transport between the endoplasmic reticulum (ER) and Golgi and observed that SEC22-GFP was retained in the cis-Golgi in the Δrud3 mutant. RUD3 contains the coiled coil (CC), GRAB-associated 2 (GA2), GRIP-related Arf binding (GRAB), and GRAB-associated 1 (GA1) domains, which except for GA1, are indispensable for normal localization and function of RUD3, whereas only CC is essential for normal RUD3-RUD3 interaction. Together, these results demonstrate how the golgin protein RUD3 mediates retrograde trafficking in the ER-to-Golgi pathway and is necessary for growth, ascospore discharge, DON biosynthesis, and pathogenicity in F. graminearum. IMPORTANCE Fusarium head blight (FHB) caused by the fungal pathogen Fusarium graminearum is an economically important disease of wheat and other small grain cereal crops worldwide, and limited effective control strategies are available. A better understanding of the regulation mechanisms of F. graminearum development, deoxynivalenol (DON) biosynthesis, and pathogenicity is therefore important for the development of effective control management of this disease. Golgins are attached via their extreme carboxy terminus to the Golgi membrane and are involved in vesicle trafficking and organelle maintenance in eukaryotic cells. In this study, we systematically characterized a highly conserved Golgin protein, RUD3, and found that it is required for vegetative growth, ascospore discharge, DON production, and pathogenicity in F. graminearum. Our findings provide a comprehensive characterization of the golgin family protein RUD3 in plant-pathogenic fungus, which could help to identify a new potential target for effective control of this devastating disease.

scholarly journals Entamoeba histolyticaAlters Ileal Paneth Cell Functions in Intact and Muc2 Mucin Deficiency

2018 ◽  
Vol 86 (7) ◽  
pp. e00208-18 ◽  
Author(s):  
Eduardo R. Cobo ◽  
Ravi Holani ◽  
France Moreau ◽  
Kiminori Nakamura ◽  
Tokiyoshi Ayabe ◽  
...  
Keyword(s):  
Entamoeba Histolytica ◽  
Host Defense ◽  
Cysteine Proteinase ◽  
Paneth Cell ◽  
Active Form ◽  
Paneth Cells ◽  
Content Type ◽  
Cell Functions ◽  
Pathogen Invasion ◽  
And Function

ABSTRACTEnteric α-defensins, termed cryptdins (Crps) in mice, and lysozymes secreted by Paneth cells contribute to innate host defense in the ileum. Antimicrobial factors, including lysozymes and β-defensins, are often embedded in luminal glycosylated colonic Muc2 mucin secreted by goblet cells that form the protective mucus layer critical for gut homeostasis and pathogen invasion. In this study, we investigated ileal innate immunity againstEntamoeba histolytica, the causative agent of intestinal amebiasis, by inoculating parasites in closed ileal loops inMuc2+/+andMuc2−/−littermates and quantifying Paneth cell localization (lysozyme expression) and function (Crp secretion). Relative toMuc2+/+littermates,Muc2−/−littermates showed a disorganized mislocalization of Paneth cells that was diffusely distributed, with elevated lysozyme secretion in the crypts and on villi in response toE. histolytica. Inhibition ofE. histolyticaGal/GalNAc lectin (Gal-lectin) binding with exogenous galactose andEntamoeba histolyticacysteine proteinase 5 (EhCP5)-negativeE. histolyticahad no effect on parasite-induced erratic Paneth cell lysozyme synthesis. Although the basal ileal expression ofCrpgenes was unaffected inMuc2−/−mice in response toE. histolytica, there was a robust release of proinflammatory cytokines and Crp peptide secretions in luminal exudates that was also present in the colon. Interestingly,E. histolytica-secreted cysteine proteinases cleaved the proregion of Crp4 but not the active form. These findings define Muc2 mucin as an essential component of ileal barrier function that regulates the localization and function of Paneth cells critical for host defense against microbes.

scholarly journals Functional Characterization of Entamoeba histolytica Argonaute Proteins Reveals a Repetitive DR-Rich Motif Region That Controls Nuclear Localization

mSphere ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Hanbang Zhang ◽  
Vy Tran ◽  
Dipak Manna ◽  
Gretchen Ehrenkaufer ◽  
Upinder Singh
Keyword(s):  
Gene Silencing ◽  
Entamoeba Histolytica ◽  
Nuclear Localization ◽  
Functional Characterization ◽  
Protozoan Parasite ◽  
Rnai Pathway ◽  
Content Type ◽  
Localization Signal ◽  
Response To Stress ◽  
Paz Domain

ABSTRACT The RNA interference (RNAi) pathway regulates gene expression in many eukaryotic organisms. Argonaute (Ago) proteins, together with bound small RNAs (sRNAs), are key effectors that mediate gene silencing function. However, there is limited knowledge of Ago proteins and their functions in nonmodel systems. In the protozoan parasite Entamoeba histolytica, RNAi is a robust means for stable gene silencing mediated via large populations of antisense sRNAs. Here, we report functional characterization of three Ago proteins in E. histolytica (EhAgo2-1, EhAgo2-2, and EhAgo2-3). Our data show that each EhAgo protein has a distinct subcellular localization and binds 27-nucleotide (nt) sRNAs and that the localization of EhAgo proteins is altered in response to stress conditions. Via mutagenesis analyses, we demonstrated that the Ago PAZ (Piwi/Argonaute/Zwille) domain in all three EhAgos is essential for sRNA binding. With mutation of the PAZ domain in EhAgo2-2, there was no effect on the nuclear localization of the protein but a strong phenotype and a growth defect. We further show that EhAgo2-2 contains an unusual repetitive DR-rich (aspartic acid, arginine-rich) motif region which functions as a nuclear localization signal (NLS) and is both necessary and sufficient to mediate nuclear localization. Overall, our data delineate the localization and sRNA binding features of the three E. histolytica Ago proteins and demonstrate that the PAZ domain is necessary for sRNA binding. The repetitive DR-rich motif region in EhAgo2-2 has not previously been defined in other systems, which adds to the novel observations that can be made when studies of the RNAi pathway are extended to nonmodel systems. IMPORTANCE The protozoan parasite Entamoeba histolytica, which causes amebiasis and affects over 50 million people worldwide, contains an important RNAi pathway for gene silencing. Gene silencing via the RNAi pathway is mediated by the Argonaute (Ago) proteins. However, we lack knowledge on Ago function(s) in this nonmodel system. In this paper, we discovered that three E. histolytica Ago proteins (EhAgo2-1, EhAgo2-2, and EhAgo2-3) all bind 27-nt small RNAs and have distinct subcellular localizations, which change in response to stress conditions. The EhAgos bind small RNA populations via their PAZ domains. An unusual repetitive DR-rich motif region is identified in EhAgo2-2 that functions as a nuclear localization signal. Our results show for the first time an active nuclear transport process of the EhAgo2-2 RNA-induced silencing complex (RISC) in this parasite. These data add to the novel observations that can be made when studies of the RNAi pathway are extended to nonmodel systems.

P159 PHENOTYPIC CHARACTERIZATION OF INFLAMMATORY BOWEL DISEASE BIOPSIES REVEAL THAT MAST CELLS ARE SIGNIFICANTLY ELEVATED AND ACTIVATED IN PATIENTS WITH ULCERATIVE COLITIS

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S33-S34
Author(s):  
Bradford Youngblood ◽  
Tina Davis ◽  
Julia Schanin ◽  
Melina Butuci ◽  
Emily Brock ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Mast Cell ◽  
Mast Cells ◽  
Inhibitory Activity ◽  
Human Colon ◽  
Colonic Tissue ◽  
Colon Tissue ◽  
Inflammatory Bowel

Abstract Rationale Accumulation and activation of mast cells and eosinophils have been implicated in the pathogenesis of several chronic inflammatory gastrointestinal (GI) diseases, including eosinophilic gastrointestinal diseases (EGIDs) and inflammatory bowel disease (IBD). Despite the strong association of mast cell and eosinophil numbers and activation with the pathogenesis of IBD, no further characterization of these cells has been performed. Current treatment options for IBD include aminosalicylates, antibiotics, immunomodulators, biologic agents and small molecules. These therapies are only moderately effective. A significant proportion of patients fail to respond, do not fully respond, or lose response over time. Therefore, there is significant need for more selective and effective therapy options. Siglec-8 is an inhibitory receptor selectively expressed on human eosinophils and mast cells and represents a novel target for the treatment of IBD with the anti-Siglec-8 mAb, antolimab (AK002). We aimed to quantify and evaluate the activation state of mast cells and eosinophils in colonic tissue from IBD or non-diseased patients. In addition, we quantified the production of TNFa from human colon tissue mast cells and evaluated the inhibitory activity of antolimab (AK002) on these cells. Methods Single-cell suspensions were prepared by enzymatic digestion of fresh colonic biopsies from patients clinically diagnosed with IBD (n=29) or non-diseased control tissues (n=16). Multi-color flow cytometry was performed to identify major immune cell populations and evaluate the activation state of mast cells and eosinophils. Mast cells were FACS-sorted from human colon tissue to evaluate cytokine production and inhibitory activity of antolimab. Results The percentage of mast cells and the expression of the mast cell degranulation marker CD107a were significantly increased in ulcerative colitis (UC) patient biopsy tissue compared to Crohn’s disease (CD) and non-diseased colonic tissue (Figure 1A and B). Furthermore, FACS-sorted mast cells from human colon tissue produced significant quantities of TNFa that was reduced after ex vivo antolimab treatment. Colonic tissue eosinophils were also elevated in a subset of UC and CD patient biopsies, and all UC and CD tissue eosinophils displayed increased expression of the activation marker CD11b compared to control colonic tissue. Conclusions Mast cells and eosinophils may play a significant role in driving the pathogenesis of ulcerative colitis through the production of inflammatory mediators. The high expression of Siglec-8 and the inhibitory activity against mast cells suggests that antibodies that target this receptor, such as antolimab (AK002) represent a potential novel approach for the treatment of IBD.

Sign in / Sign up

Export Citation Format

Share Document