Analysis of the survival of mature human eosinophils: interleukin-5 prevents apoptosis in mature human eosinophils

Yamaguchi, Yoshiko; Suda, Toshio; Ohta, Shigeyuki; Tominaga, Keiichiro; Miura, Yasusada; Kasahara, Takeaki

doi:10.1182/blood.v78.10.2542.bloodjournal78102542

Cited by 76 publications

(69 citation statements)

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“…Next, we incubated freshly isolated peripheral eosinophils with IL-5, IL-13, eotaxin-3 or recombinant periostin, either singly or in combination, and assessed cell viability via 4',6-diamidino-2-phenylindole (DAPI) exclusion after 24 h in culture. As expected, eosinophils maintained in media without supplemental cytokines displayed high rates of cell death (35.4%, range 25.2-41.4%) after 24 h. In contrast, and as previously described, 33 IL-5 enhanced eosinophil survival, with significantly less cell death (11.5%, range 8.6-15.9%) after 24 h in culture (Figure 5a, b). Neither IL-13 nor eotaxin-3 enhanced eosinophil survival compared to media alone, with generally up to 40% of cells exhibiting permeability to DAPI after 24 h (Figure 5b).…”

Section: Periostin Enhances Eosinophil Survival Through Amsupporting

confidence: 86%

Integrin αM activation and upregulation on esophageal eosinophils and periostin‐mediated eosinophil survival in eosinophilic esophagitis

et al. 2018

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Eosinophilic esophagitis (EoE) is an increasingly recognized allergic disease associated with dysphagia and esophageal fibrosis. We aimed to determine expression patterns of specific eosinophil integrins that promote eosinophilic infiltration of the esophageal epithelium, and to determine how key EoE-related cytokines influence eosinophil activation and survival. Esophageal and peripheral eosinophils were isolated from 20 adult subjects with EoE for immunophenotyping and integrin profiling using multicolor flow cytometry and immunohistochemistry. Expression signatures of eosinophil integrins were further assessed by immunohistochemistry using serial sections of esophageal biopsy specimens. Purified eosinophils were used to assess the effect of EoE-relevant cytokines and recombinant periostin on expression of known eosinophil integrins and eosinophil survival and activation. We found that resting eosinophils express high levels of the β2-pairing integrins αL and αM, and lower levels of α4, α6 and α4β7. The migration of peripheral eosinophils to the esophagus is characterized by the specific induction of αM, and a significant increase in the proportion of αM in high-activity conformation. Periostin, a secreted extracellular matrix protein that is significantly overexpressed in EoE, enhances eosinophil survival, and this effect is mediated by αM interaction. Integrin αM is a specific marker of activated tissue eosinophils in EoE, and promotes eosinophil survival through interactions with periostin. The ability of αMβ2 to mediate eosinophil tissue residency via periostin represents a key mechanism for disease development and a potential therapeutic target in EoE.

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Section: Periostin Enhances Eosinophil Survival Through Amsupporting

confidence: 86%

Integrin αM activation and upregulation on esophageal eosinophils and periostin‐mediated eosinophil survival in eosinophilic esophagitis

et al. 2018

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“…We next looked for AT-specific mechanisms to explain the local increase in eosinophil number, namely, the expression of the eosinophil growth factor, IL-5, as well as eosinophil chemokines CCL11, CCL24, CCL3, and CCL5. IL-5 is strongly linked with eosinophil function, as it regulates cellular differentiation, proliferation/apoptosis, activation, and accumulation [22,23] and was recently shown to contribute to eosinophil accumulation in AT [15]. We found that eAT of obese CCR2 2/2 mice had significantly higher Il5 expression than that of WT counterparts (Fig.…”

Section: Increased Eosinophils In At Correlate With Increased Expressmentioning

confidence: 52%

CCR2 deficiency leads to increased eosinophils, alternative macrophage activation, and type 2 cytokine expression in adipose tissue

Bolus

Gutierrez

Kennedy

et al. 2015

Journal of Leukocyte Biology

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Adipose tissue (AT) inflammation during obesity is mediated by immune cells and closely correlates with systemic insulin resistance. In lean AT, eosinophils are present in low but significant numbers and capable of promoting alternative macrophage activation in an IL-4/IL-13-dependent manner. In WT mice, obesity causes the proportion of AT eosinophils to decline, concomitant with inflammation and classical activation of AT macrophages. In this study, we show that CCR2 deficiency leads to increased eosinophil accumulation in AT. Furthermore, in contrast to WT mice, the increase in eosinophils in CCR2(-/-) AT is sustained and even amplified during obesity. Interestingly, a significant portion of eosinophils is found in CLSs in AT of obese CCR2(-/-) mice, which is the first time eosinophils have been shown to localize to these inflammatory hot spots. CCR2(-/-) bone marrow precursors displayed increased expression of various key eosinophil genes during in vitro differentiation to eosinophils, suggesting a potentially altered eosinophil phenotype in the absence of CCR2. In addition, the proportion of eosinophils in AT positively correlated with local expression of Il5, a potent eosinophil stimulator. The increase in eosinophils in CCR2(-/-) mice was detected in all white fat pads analyzed and in the peritoneal cavity but not in bone marrow, blood, spleen, or liver. In AT of CCR2(-/-) mice, an increased eosinophil number positively correlated with M2-like macrophages, expression of the Treg marker Foxp3, and type 2 cytokines, Il4, Il5, and Il13. This is the first study to link CCR2 function with regulation of AT eosinophil accumulation.

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“…Unlike GM-CSF and IL-3, IL-5 is a cytokine that exhibits lineage restriction. It stimulates the proliferation, maturation, and functional activation of eosinophils (151)(152)(153)(154)(155)(156) and basophils (157)(158)(159). The major cellular source of IL-5 is T cells (160), although mast cells and to some extent eosinophils (160, 161) also produce IL-5.…”

Section: Il-5 and Its Receptormentioning

confidence: 99%

The GM–CSF/IL‐3/IL‐5 cytokine receptor family: from ligand recognition to initiation of signaling

Broughton

Dhagat

Hercus

et al. 2012

Immunological Reviews

209

162

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Granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5 are members of a discrete family of cytokines that regulates the growth, differentiation, migration and effector function activities of many hematopoietic cells and immunocytes. These cytokines are involved in normal responses to infectious agents, bridging innate and adaptive immunity. However, in certain cases, the overexpression of these cytokines or their receptors can lead to excessive or aberrant initiation of signaling resulting in pathological conditions, with chronic inflammatory diseases and myeloid leukemias the most notable examples. Recent crystal structures of the GM-CSF receptor ternary complex and the IL-5 binary complex have revealed new paradigms of cytokine receptor activation. Together with a wealth of associated structure-function studies, they have significantly enhanced our understanding of how these receptors recognize cytokines and initiate signals across cell membranes. Importantly, these structures provide opportunities for structure-based approaches for the discovery of novel and disease-specific therapeutics. In addition, recent biochemical evidence has suggested that the GM-CSF/IL-3/IL-5 receptor family is capable of interacting productively with other membrane proteins at the cell surface. Such interactions may afford additional or unique biological activities and might be harnessed for selective modulation of the function of these receptors in disease.

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Analysis of the survival of mature human eosinophils: interleukin-5 prevents apoptosis in mature human eosinophils

Cited by 76 publications

References 0 publications

Integrin αM activation and upregulation on esophageal eosinophils and periostin‐mediated eosinophil survival in eosinophilic esophagitis

Integrin αM activation and upregulation on esophageal eosinophils and periostin‐mediated eosinophil survival in eosinophilic esophagitis

CCR2 deficiency leads to increased eosinophils, alternative macrophage activation, and type 2 cytokine expression in adipose tissue

The GM–CSF/IL‐3/IL‐5 cytokine receptor family: from ligand recognition to initiation of signaling

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