Eosinophil chemotaxis assay in nasal polyps by using a novel optical device EZ-TAXIScan: Role of CC-chemokine receptor 3

Saito, Hidekazu; Honda, Kazuo; Asaka, Chikara; Ueki, Shigeharu; Ishikawa, Kazuo

doi:10.1016/j.alit.2016.01.001

Cited by 13 publications

(8 citation statements)

References 24 publications

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“…The presence of mucosal eosinophilia is correlated with disease severity and clinically distinct subsets of CRS [15–17]. The pathophysiology of tissue eosinophilia is incompletely known, but Th2 cytokines including IL-5 and eotaxins play an indispensable role in eosinophil-selective accumulation, similar to other allergic diseases [12, 18]. Of note, approximately 30 % of tissue eosinophils in CRSwNP exhibit ultrastructural evidence of cytolysis [19].…”

Section: Lessons From Chronic Rhinosinusitis: Pathogenesis Of Eosinopmentioning

confidence: 99%

Eosinophil ETosis and DNA Traps: a New Look at Eosinophilic Inflammation

Ueki

Tokunaga

Fujieda

et al. 2016

Curr Allergy Asthma Rep

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The traditional paradigm of eosinophils as end-stage damaging cells has mainly relied on their release of cytotoxic proteins. Cytokine-induced cell survival and secretion of granular contents from tissue-dwelling eosinophil are thought to be important mechanisms for eosinophilic inflammatory disorders, although the occurrence of cytolysis and its products (i.e., free extracellular granules) has been observed in affected lesions. Recent evidence indicates that activated eosinophils can exhibit a non-apoptotic cell death pathway, namely extracellular trap cell death (ETosis) that mediates the eosinophil cytolytic degranulation. Here, we discuss the current concept of eosinophil ETosis which provides a new look at eosinophilic inflammation. Lessons from eosinophilic chronic rhinosinusitis revealed that ETosis-derived DNA traps, composed of stable web-like chromatin, contribute to the properties of highly viscous eosinophilic mucin and impairments in its clearance. Intact granules entrapped in DNA traps are causing long-lasting inflammation but also might have immunoregulatory roles. Eosinophils possess a way to have post-postmortem impacts on innate immunity, local immune response, sterile inflammation, and tissue damage.

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Section: Lessons From Chronic Rhinosinusitis: Pathogenesis Of Eosinopmentioning

confidence: 99%

Eosinophil ETosis and DNA Traps: a New Look at Eosinophilic Inflammation

Ueki

Tokunaga

Fujieda

et al. 2016

Curr Allergy Asthma Rep

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“…In our study, we found that the control or surrounding colonic tissue of the distal colon harbors 13-20 eosinophils/HPF, whereas the polyp tissue showed a significantly higher frequency of cells (43,06+/-22,32 eosinophils/HPF), along with significantly increased levels of CCL26 in the epithelial compartment. Other authors have reported similar results in nasal polyps, with a high tissue content of chemokines and high eosinophil count (13). Furthermore, CCL26 has also been described as produced by human bronchial epithelial cells (14) and keratinocytes (15) and its imbalanced secretion, probably due to an overexpression of type-2 cytokines, was implicated in atopic dermatitis and asthma (16)(17)(18).…”

Section: Discussionmentioning

confidence: 63%

Type-2 Cytokines Promote the Secretion of the Eosinophil–Attractant CCL26 by Intestinal Epithelial Cells in Food-Sensitized Patients

et al. 2022

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Several inflammatory processes of the bowel are characterized by an accumulation of eosinophils at inflammation sites. The mechanisms that govern mucosal infiltration with eosinophils are not fully understood. In this work, we studied the colorectal polyp-confined tissue containing eosinophils and we hypothesized that intestinal epithelial cells are the cell source of eotaxin-3 or CCL26, a potent chemoattractant for eosinophils. We analyzed colorectal polyps (n=50) from pediatric patients with rectal bleeding by H&E staining and eosin staining, and different pro-inflammatory cytokines were assessed by RT-qPCR and ELISA. IgE and CCL26 were investigated by RT-qPCR, ELISA and confocal microscopy. Finally, the intracellular signaling pathway that mediates the CCL26 production was analyzed using a kinase array and immunoblotting in human intestinal Caco-2 cell line. We found a dense cell agglomeration within the polyps, with a significantly higher frequency of eosinophils than in control adjacent tissue. IL-4 and IL-13 were significantly up-regulated in polyps and CCL26 was elevated in the epithelial compartment. Experiments with Caco-2 cells showed that the type-2 cytokine IL-13 increased STAT3 and STAT6 phosphorylation and eotaxin-3 secretion. The addition of the blocking antibody Dupilumab or the inhibitor Ruxolitinib to the cytokine-stimulated Caco-2 cells diminished the CCL26 secretion to basal levels in a dose-dependent manner. In conclusion, our findings demonstrate a high frequency of eosinophils, and elevated levels of type-2 cytokines and eotaxin-3 in the inflammatory stroma of colorectal polyps from pediatric patients. Polyp epithelial cells showed to be the main cell source of CCL26, and IL-13 was the main trigger of this chemokine through the activation of the STAT3/STAT6/JAK1-2 pathway. We suggest that the epithelial compartment actively participates in the recruitment of eosinophils to the colonic polyp-confined inflammatory environment.

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“…Previous literature has reported several factors implicated in eosinophil development, homing, and survival, including Eotaxin 19,20 , IL-5 [21][22][23][24] , and others 7,8,25 . To determine which factors may be influencing eosinophil development and survival in the IL7R mutant mice, we collected serum from WT and mutant mice and compared the relative concentration of several cytokines.…”

Section: Il7r Deletion Caused Alterations In Cytokines Involved In Mymentioning

confidence: 99%

“…We found that two known eosinophil regulators, Eotaxin and IL-5, were reduced in the IL7Rα -/mice. Both of these cytokines are known to be secreted by lymphoid cells to promote eosinophil development, homing, and survival 19,20,[22][23][24]29 . Additionally, as previously reported 7 , we observed that IL-7 was upregulated in the IL7R -/mice, likely due to unbound excess IL-7 in the absence of lymphoid cells.…”

Section: Il7r Deletion Caused Alterations In Cytokines Involved In Mymentioning

confidence: 99%

Interleukin 7 receptor (IL7R) is required for myeloid cell homeostasis and reconstitution by hematopoietic stem cells

Cool

Worthington

Poscablo

et al. 2020

Preprint

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Respiratory diseases are a leading cause of death worldwide, with highly varied vulnerability to disease between individuals. The underlying reasons of disease susceptibility are unknown, but often include a variable immune response in lungs. Recently, we identified a surprising novel role of the interleukin 7 receptor (IL7R), a primarily lymphoid-associated regulator, in fetal-specified, lung-resident macrophage development. Here, we report that traditional, hematopoietic stem cell-derived myeloid cells in the adult lung, peripheral blood, and bone marrow also depend on IL7R expression. Using single and double germline knockout models, we found that eosinophil numbers were reduced upon deletion of IL7Rα. We then employed two Cre recombinase models in lineage tracing experiments to test whether these cells developed through an IL7Rα+ pathway. Despite the impact of IL7Rα deletion, IL7R-Cre labeled only a minimal fraction of eosinophils. We therefore examined the intrinsic versus extrinsic requirement for IL7R in the production of eosinophils using reciprocal hematopoietic stem cell transplantation assays. These assays revealed that extrinsic, but not eosinophil-intrinsic, IL7R is required for eosinophil reconstitution by HSCs in the adult lung. To determine which external factors may be influencing eosinophil development and survival, we performed a cytokine array analysis between wild-type and IL7Rα-deficient mice and found several differentially regulated proteins. These findings expand upon our previous publication that IL7R is required not only for proper lymphoid cell development and homeostasis, but also for myeloid cell homeostasis in tissues.HighlightsLoss of IL7Rα resulted in significantly fewer eosinophils in adult miceIL7R-Cre lineage tracing revealed minimal labeling of eosinophilsIL7Rα-deficient HSCs robustly reconstituted eosinophils in a WT hostWT HSCs failed to fully reconstitute eosinophils in IL7Rα-/- hostsSeveral cytokines are differentially expressed in WT and IL7Rα-deficient mice

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Eosinophil chemotaxis assay in nasal polyps by using a novel optical device EZ-TAXIScan: Role of CC-chemokine receptor 3

Abstract: The CCR3 pathway may play an important role in the pathogenesis of eosinophil recruitment in nasal polyps through selective eosinophil chemotaxis.

Cited by 13 publications

References 24 publications

Eosinophil ETosis and DNA Traps: a New Look at Eosinophilic Inflammation

Eosinophil ETosis and DNA Traps: a New Look at Eosinophilic Inflammation

Type-2 Cytokines Promote the Secretion of the Eosinophil–Attractant CCL26 by Intestinal Epithelial Cells in Food-Sensitized Patients

Interleukin 7 receptor (IL7R) is required for myeloid cell homeostasis and reconstitution by hematopoietic stem cells

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