Eosinophils in Inflammatory Bowel Disease

Filippone, Rhiannon T; Sahakian, Lauren; Apostolopoulos, Vasso; Nurgali, Kulmira

doi:10.1093/ibd/izz024

Cited by 56 publications

(49 citation statements)

References 196 publications

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“…Eosinophilia has been recognized as an important factor in the pathogenesis of Mcd (4). Eos are a fraction of the end effector cells of Mcd, as well as many other inflammatory disorders, such as allergic asthma (26) and inflammatory bowel disease (27) The present data show a negative correlation between IL-5 and Eo apoptosis in the heart tissues. IL-5 is an essential molecule for the Eo differentiation and survival (28).…”

Section: Discussionsupporting

confidence: 53%

RETRACTED: Inhibition of Bcl2L12 Attenuates Eosinophilia-Related Inflammation in the Heart

et al. 2020

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Background: The eosinophilic inflammation plays a critical role in myocarditis (Mcd); its underlying mechanism remains to be further elucidated. This study aims to investigate the role of Bcl2-like protein 12 (Bcl2L12) in inducing the defects of apoptosis in eosinophils (Eos) of the heart tissues. Methods: Human explant heart samples were collected. Eosinophilia and myocarditis (Mcd)-like inflammation were induced in the mouse heart by immunizing with murine cardiac α-myosin heavy chain (MyHCα) peptides. Results: Markedly more Eos were observed in heart tissues from patients with Mcd than those from patients with dilated cardiomyopathy. Eos isolated from Mcd hearts showed the signs of apoptosis defects. The Eo counts in the Mcd heart tissues were positively correlated with the Bcl2L12 expression in Eos isolated from the heart tissues. Exposure to interleukin 5 in the culture induced the expression of Bcl2L12 in Eos. Bcl2L12 bound c-Myc, the transcription factor of Fas ligand (FasL), to prevent c-Myc from binding to the FasL promoter, to restrict the FasL gene transcription in Eos. Inhibition of Bcl2L12 prevented the induction of eosinophilia and Mcd-like inflammation in the mouse heart. Conclusions: The Bcl2L12 expression contributes to apoptosis defects in Eos of the Mcd heart. Blocking Bcl2L12 prevents the eosinophilia induction and alleviates Mcd-like inflammation in mice.

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Section: Discussionsupporting

confidence: 53%

RETRACTED: Inhibition of Bcl2L12 Attenuates Eosinophilia-Related Inflammation in the Heart

et al. 2020

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“…For example, intestinal eosinophils and eosinophil peroxidase (EPO) are critical for the initiation of Th2 responses (IgE) to food allergens in the gastrointestinal (GI) tract (6,9). Furthermore, intestinal accumulation of eosinophils has been associated with the severity of inflammatory bowel disease (IBD) (10,11). Conversely, intestinal eosinophils secrete large quantities of IL-1 receptor antagonist, thus reducing inflammation in IBD (12,13).…”

Section: Introductionmentioning

confidence: 99%

Microbial Regulation of Enteric Eosinophils and Its Impact on Tissue Remodeling and Th2 Immunity

et al. 2020

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Eosinophils have emerged as multifaceted cells that contribute to tissue homeostasis. However, the impact of the microbiota on their frequency and function at mucosal sites remains unclear. Here, we investigated the role of the microbiota in the regulation of enteric eosinophils. We found that small intestinal (SI) eosinophilia was significantly greater in germ-free (GF) mice compared to specific pathogen free (SPF) controls. This was associated with changes in the production of enteric signals that regulate eosinophil attraction and survival, and was fully reversed by complex colonization. Additionally, SI eosinophils of GF mice exhibited more cytoplasmic protrusions and less granule content than SPF controls. Lastly, we generated a novel strain of eosinophil-deficient GF mice. These mice displayed intestinal fibrosis and were less prone to allergic sensitization as compared to GF controls. Overall, our study demonstrates that commensal microbes regulate intestinal eosinophil frequency and function, which impacts tissue repair and allergic sensitization to food antigens. These data support a critical interplay between the commensal microbiota and intestinal eosinophils in shaping homeostatic, innate, and adaptive immune processes in health and disease.

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“…Tissue-resident eosinophils are activated in inflammatory diseases of the gastrointestinal tract such as IBD [28] and others such as microscopic colitis [32]. After activation, eosinophils release preformed granular proteins and de novo produced lipid mediators and cytokines [33]. Eosinophil granular proteins such as eosinophil cationic protein (ECP), eosinophil protein X (EPX) or eosinophil-derived neurotoxin are also released in the intestinal lumen and can be detected in feces.…”

Section: Introductionmentioning

confidence: 99%

“…ECP, which was studied here, belongs to the ribonuclease family. ECP plays a role in RNA metabolism, possesses bactericidal and helmintho-toxic activity and induces host cell apoptosis and necrosis [33,34].…”

Section: Introductionmentioning

confidence: 99%

Fecal Eosinophil Cationic Protein Is a Diagnostic and Predictive Biomarker in Young Adults with Inflammatory Bowel Disease

Abedin

Seemann

Kleinfeld

et al. 2019

JCM

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Background and Aims: Fecal biomarkers are important non-invasive markers monitoring disease activity in inflammatory bowel disease (IBD). We compared the significance of fecal eosinophil cationic protein (fECP) and fecal calprotectin (fCal). Methods: fECP and fCal were measured in patients with Crohn’s disease (CD, n = 97), ulcerative colitis (UC, n = 53), Clostridioides difficile infection (CDI, n = 9), primary food allergy (PFA, n = 11), pollen-associated food allergy (n = 25) and non-inflammatory controls (n = 78). Results were correlated with clinical and endoscopic IBD activity scores. Results: fECP was significantly elevated in CD, UC, CDI and PFA compared to controls. fCal was significantly increased in CD, UC and CDI. fECP had lower diagnostic accuracy than fCal (area under the curve (AUC) = 0.88) in differentiating between endoscopically active and inactive patients with IBD (AUC = 0.77, ROC analysis). In contrast to fCal, fECP correlated negatively with age and levels were also elevated in clinically and endoscopically inactive patients with IBD <45 years (endoscopically inactive IBD vs controls; AUC for fECP = 0.86; AUC for fCal = 0.62). However, in those patients with low inflammatory activity (fCal <250 mg/kg), high fECP indicated the need for treatment modification or surgery (fECP <200 µg/kg = 22%; 200–600 µg/kg = 44%; >600 µg/kg = 82%) at month 48 of follow-up. Conclusions: fECP is a diagnostic and prognostic marker in young patients with IBD in remission.

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Eosinophils in Inflammatory Bowel Disease

Cited by 56 publications

References 196 publications

RETRACTED: Inhibition of Bcl2L12 Attenuates Eosinophilia-Related Inflammation in the Heart

RETRACTED: Inhibition of Bcl2L12 Attenuates Eosinophilia-Related Inflammation in the Heart

Microbial Regulation of Enteric Eosinophils and Its Impact on Tissue Remodeling and Th2 Immunity

Fecal Eosinophil Cationic Protein Is a Diagnostic and Predictive Biomarker in Young Adults with Inflammatory Bowel Disease

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