Eosinophil associated genes in the inflammatory bowel disease 4 region: Correlation to inflammatory bowel disease revealed

Blom, Kristin; Rubin, Jenny; Halfvarson, Jonas; Törkvist, Leif; Rönnblom, Anders; Sangfelt, Per; Lördal, Mikael; Jönsson, Ulla-Britt; Sjöqvist, Urban; Håkansson, Lena; Carlson, Marie

doi:10.3748/wjg.v18.i44.6409

Cited by 14 publications

(16 citation statements)

References 54 publications

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“…This polymorphism changes an arginine (base at 434 is G) at position 97 to threonine (base at 434 is C). The ECP 434(GϾC) polymorphism correlates with the natural course of Schistosoma mansoni infection (78) and with inflammatory bowel disease in an age-and gender-dependent manner (79). These ECP genotypes also show associations with the symptoms of allergy and asthma (80,81).…”

Section: Eosinophil Cationic Proteinmentioning

confidence: 99%

Eosinophil Granule Proteins: Form and Function

Acharya

Ackerman

2014

Journal of Biological Chemistry

431

364

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Experimental and clinical data strongly support a role for the eosinophil in the pathogenesis of asthma, allergic and parasitic diseases, and hypereosinophilic syndromes, in addition to more recently identified immunomodulatory roles in shaping innate host defense, adaptive immunity, tissue repair/remodeling, and maintenance of normal tissue homeostasis. A seminal finding was the dependence of allergic airway inflammation on eosinophil-induced recruitment of Th2-polarized effector T-cells to the lung, providing a missing link between these innate immune effectors (eosinophils) and adaptive T-cell responses. Eosinophils come equipped with preformed enzymatic and nonenzymatic cationic proteins, stored in and selectively secreted from their large secondary (specific) granules. These proteins contribute to the functions of the eosinophil in airway inflammation, tissue damage, and remodeling in the asthmatic diathesis. Studies using eosinophil-deficient mouse models, including eosinophil-derived granule protein double knock-out mice (major basic protein-1/eosinophil peroxidase dual gene deletion) show that eosinophils are required for all major hallmarks of asthma pathophysiology: airway epithelial damage and hyperreactivity, and airway remodeling including smooth muscle hyperplasia and subepithelial fibrosis. Here we review key molecular aspects of these eosinophil-derived granule proteins in terms of structure-function relationships to advance understanding of their roles in eosinophil cell biology, molecular biology, and immunobiology in health and disease.

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Section: Eosinophil Cationic Proteinmentioning

confidence: 99%

Eosinophil Granule Proteins: Form and Function

Acharya

Ackerman

2014

Journal of Biological Chemistry

431

364

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“…A growing number of studies support a functional role for eosinophils in IBD [11][12][13][14]. Eosinophil numbers were increased in active disease compared with normal control subjects [10].…”

Section: Introductionmentioning

confidence: 99%

Regulation of eotaxin-3/CC chemokine ligand 26 expression by T helper type 2 cytokines in human colonic myofibroblasts

Takahashi

Imaeda

Fujimoto

et al. 2013

Clinical and Experimental Immunology

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SummaryEotaxins induce the trafficking of eosinophils to the sites of inflammation via CC chemokine receptor 3 (CCR3). In this study, we investigated eotaxin-3/CC chemokine ligand 26 (CCL26) expression in the inflamed mucosa of patients with inflammatory bowel disease (IBD), and characterized the molecular mechanisms responsible for eotaxin-3 expression in human colonic myofibroblasts. Eotaxin-3 mRNA and protein expression was evaluated by real time-polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Eotaxin-3 mRNA expression was elevated significantly in the active lesions of ulcerative colitis (UC) patients. Significant elevations were also observed in the active lesions of Crohn's disease (CD) patients, but this was significantly lower than that detected in the active UC lesions. There were no significant increases in the inactive lesions of UC or CD patients. Colonic myofibroblasts were identified as a major source of eotaxin-3 in the colonic mucosa, and interleukin (IL)-4 and IL-13 enhanced eotaxin-3 mRNA and protein expression significantly in these cells. There was a significant positive correlation between mucosal eotaxin-3 and IL-4 mRNA expression in the active lesions of IBD patients. The IL-4-and IL-13-induced eotaxin-3 mRNA expression was regulated by the signal transducer and activator of transcription-6 (STAT-6) and suppressor of cytokine signalling (SOCS)1-mediated pathways. Interferon (IFN)-g acts as a negative regulator on the IL-4-and IL-13-induced eotaxin-3 expression via STAT-1 activation. Eotaxin-3 expression was elevated specifically in the active lesions of IBD, in particular UC. Eotaxin-3 derived from colonic myofibroblasts may play an important role in the pathophysiology of UC.

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“…We found that this deficiency was closely related to the genetic expression of the EDN gene since those infected by L. donovani predominantly carried the GG genotype of the EDN405 gene polymorphism. An association between this gene polymorphism and the eosinophil content of EDN has also been shown in Scandinavian populations , which contradicts the possibilities that this association is governed by differences in ethnicities. Rather this association seems related to the development of specific diseases and in this study to the lower resistance to infections by L. donovani .…”

Section: Discussionmentioning

confidence: 99%

The genetically determined production of the alarmin eosinophil‐derived neurotoxin is reduced in visceral leishmaniasis

Blom

Elshafie

Jönsson

et al. 2017

APMIS

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Blom K, Elshafie AI, J€ onsson U-B, R€ onnelid J, H akansson LD, Venge P. The genetically determined production of the alarmin eosinophil-derived neurotoxin is reduced in visceral leishmaniasis. APMIS 2018; 126: 85-91.Visceral leishmaniasis (VL) is the most severe form of leishmaniasis. Recent findings indicate that dendritic cells have a key role in the defense against the Leishmania parasite and that the activity of this cell may be modified by the eosinophil secretory protein eosinophil-derived neurotoxin (EDN). We hypothesized that the interactions between dendritic cells and EDN might be of importance in the disease development. Cellular content of EDN was analyzed by ELISA. The single-nucleotide polymorphisms at positions 405, 416, and 1122 in the EDN gene were analyzed by real-time PCR with TaqMan Ò reagents. The study cohorts comprised 239 Sudanese subjects (65 healthy controls and 174 with VL) and 300 healthy Swedish controls. The eosinophil content of EDN was lower in VL as compared with controls (p < 0.0001). The EDN405 (G>C) genotype distribution was similar among Swedish and Sudanese controls, whereas VL subjects had a higher prevalence of the EDN405-GG genotype (p < 0.0001). The content of EDN in the eosinophils was closely linked to the EDN405 polymorphism (p = 0.0002). Our findings suggest that the predisposition to acquire VL is related to the genetic polymorphism of the EDN gene and the reduced production by the eosinophil of this gene product.

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Eosinophil associated genes in the inflammatory bowel disease 4 region: Correlation to inflammatory bowel disease revealed

Abstract: Polymorphisms of EPX and ECP are associated to IBD in an age and gender dependent manner, suggesting an essential role of eosinophils in the pathophysiology of IBD.

Cited by 14 publications

References 54 publications

Eosinophil Granule Proteins: Form and Function

Eosinophil Granule Proteins: Form and Function

Regulation of eotaxin-3/CC chemokine ligand 26 expression by T helper type 2 cytokines in human colonic myofibroblasts

The genetically determined production of the alarmin eosinophil‐derived neurotoxin is reduced in visceral leishmaniasis

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