Eosinophil function in eosinophil-associated gastrointestinal disorders

Hogan, Simon P.; Rothenberg, Marc E.

doi:10.1007/s11882-006-0013-8

Cited by 51 publications

(36 citation statements)

References 55 publications

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“…The SCIDbgMN mice utilized in these experiments were created from SCIDbg mice after X irradiation (4 Gy) and other treatments (anti-Ly6G MAb and carrageenan). Since irradiation is known to damage the intestinal epithelium, there was a concern that intestinal epithelial cellmediated innate immune responses (e.g., antimicrobial peptide production and cytokine/chemokine production) would be impaired in SCIDbgMN mice and the susceptibility of these (47), the accumulation of these cells at the inflammation site has been described (20,55). So far, the active pathological role of these cells at the C. parvum infection site is not known.…”

Section: Discussionmentioning

confidence: 99%

Cooperative Role of Macrophages and Neutrophils in Host Antiprotozoan Resistance in Mice Acutely Infected withCryptosporidium parvum

et al. 2008

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Section: Discussionmentioning

confidence: 99%

Cooperative Role of Macrophages and Neutrophils in Host Antiprotozoan Resistance in Mice Acutely Infected withCryptosporidium parvum

et al. 2008

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“…In addition, 2 PU.1 sites, a C/EBP␣ site, and, importantly, a GATA-1 site were also present, suggesting that transcription factors that play crucial roles during eosinophil differentiation may reinforce the IL-5R/syntenin pathway. 38,39 In an analogous fashion, transcription factors that control T helper cell differentiation have been shown to stimulate expression of factors that control their own activation. [40][41][42][43] We propose a model in which IL-5 via IL-5R␣/syntenin stimulates key eosinophil transcription factors, which in turn reinforce IL-5R␣ and syntenin expression as part of a positive feedback mechanism.…”

Section: Discussionmentioning

confidence: 99%

Regulation of myelopoiesis through syntenin-mediated modulation of IL-5 receptor output

Beekman

Verhagen²,

Geijsen

et al. 2009

Blood

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The granulocyte-macrophage colonystimulating factor (GM-CSF)/interleukin (IL)-3/IL-5 receptor family regulates the production and function of myeloid cells. These cytokines signal through receptor complexes that consist of unique ligandbinding ␣-chains and common signaling ␤-chains. IL-5 is distinct from IL-3 and GM-CSF in its capacity to induce eosinophil development, however, the molecular mechanisms that generate functional diversity within this receptor family are mostly unknown. Here, we characterized the selective IL-5R␣-binding adapter protein syntenin in IL-5R function. Syntenin and IL-5R␣ colocalize at the plasma membrane and in early endosomal compartments. Manipulation of syntenin expression by ectopic expression or knockdown selectively modulated IL-5R but not GM-CSF receptor signaling, and severely affected IL-5-induced eosinophil differentiation from primary human CD34 ؉ hematopoietic progenitor cells. We found syntenin upregulated during eosinophilopoiesis but down-regulated during neutropoiesis. Syntenin forms complexes with multiple IL-5R␣ chains, suggesting that synteninenhanced IL-5R output may result from stabilization of an IL-5-induced oligomeric receptor complex. These data demonstrate that cytokine-specific functions can be transduced by unique receptor ␣-chain-associating adapter proteins. (Blood. 2009;114:3917-3927) IntroductionLeukocyte functions are regulated by intracellular mechanisms that constantly integrate environmental signals. Cytokines and their receptors are key molecules in leukocyte communication that regulate hematopoiesis and immune responses. 1 Cytokine receptors have been classified on the shared use of common receptor components such as the common ␤-chain (␤c) for the granulocytemacrophage colony-stimulating factor receptor (GM-CSFR) family. 2 Tightly regulated and complex signaling networks have evolved to ensure robust cellular output of cytokine-mediated signaling input. Adapter and scaffold proteins play a decisive role in these networks by regulating the kinetics and specificity of signal transduction pathways. 3 These proteins consist of multiple protein interaction domains that lack enzymatic activity, and modulate the composition of protein complexes and thus which protein substrates are favorably targeted. Adapter molecules may allow the induction of receptor-specific signaling pathways, and cellular functions, however until now there are few examples.IL-3, IL-5, and GM-CSF are important regulators of myeloid cell differentiation and leukocyte function. 4 These cytokines bind to unique ␣-chains, and then recruit a common ␤-chain (␤c) to form high-affinity receptors. Receptor activation induces overlapping signaling pathways that depend on both ␣ and ␤c which are preassociated with Janus kinases (JAKs) that activate signal transducer and activators of transcription (STAT). 4,5 Other shared signaling pathways include the phosphoinositol-3 kinase (PI-3K)/ protein kinase B pathway (PKB/c-Akt) that is crucial for cellular survival, and mitogen-activated protein ki...

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“…These data demonstrate that IL-13 supports eosinophil migration and that CCL11 and CCL24 also are both important in promoting eosinophil infiltration [66,67] . Although patients with EoE have higher levels of several cytokines, the cytokines that are most consistently increased in this allergic disease are IL-5, IL-13 and eotaxin-3 (CCL26) [68,69] . Genome-wide microarray expression studies have shown that the gene-encoding eotaxin-3 is the most highly induced gene in EoE patients compared to healthy individuals [43] .…”

Section: Genetic Vs Environmental Etiological Factorsmentioning

confidence: 99%

Eosinophilic esophagitis: New insights in pathogenesis and therapy

Guarino

Cicala

Behar

2016

WJGPT

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Eosinophilic esophagitis (EoE) is a clinico-pathological entity with esophageal symptoms and dense esophageal eosinophilic infiltration throughout the esophagus that may persist despite treatment with proton pump inhibitors. This eosinophilic infiltration is usually absent in the stomach, small intestine and colon, although there are a number of reports of patients with a multiorgan involvement. EoE is associated with abnormalities involving TH2-dependent immunity, with multiple environmental factors strongly contributing to disease expression. The layer of the esophagus affected by the eosinophilic infiltration causes the specific symptoms. Esophageal involvement results mostly in dysphagia for solids that can be severe enough to cause recurrent esophageal obstruction with typical endoscopic features suggesting esophageal remodeling and pathological changes of eosinophilic infiltration of the mucosa, sub-epithelial fibrosis and muscle hypertrophy. This disease is frequently associated with other allergic conditions such as allergic asthma, allergic dermatitis and eosinophilia. The treatment of patients with EoE depends on the severity of the symptoms and of the inflammatory process as well as to their response to a gradual step-up treatment. The first line of treatment consists of steroid containing local inhalers. If unresponsive they are then treated with oral steroids. Intravenous interleukin blockers seem to have a consistent positive therapeutic effect. Core tip: Eosinophilic esophagitis is a clinico-pathological entity characterized by esophageal symptoms and dense esophageal eosinophilic infiltration throughout the esophagus. Our manuscript provides a deep description of the disease showing that many efforts have been made in the last decades in understanding REVIEWSubmit a

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Eosinophil function in eosinophil-associated gastrointestinal disorders

Cited by 51 publications

References 55 publications

Cooperative Role of Macrophages and Neutrophils in Host Antiprotozoan Resistance in Mice Acutely Infected withCryptosporidium parvum

Cooperative Role of Macrophages and Neutrophils in Host Antiprotozoan Resistance in Mice Acutely Infected withCryptosporidium parvum

Regulation of myelopoiesis through syntenin-mediated modulation of IL-5 receptor output

Eosinophilic esophagitis: New insights in pathogenesis and therapy

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