The multiple functions and subpopulations of eosinophils in tissues under steady-state and pathological conditions

Kanda, Akira; Yun, Yasutaka; Bui, Dan Van; Linh-Trung, Nguyen; Kobayashi, Yoshiki; Suzuki, Kensuke; Mitani, Akitoshi; Sawada, Shunsuke; Hamada, Satoko; Asako, Mikiya; Iwai, Hiroshi

doi:10.1016/j.alit.2020.11.001

Cited by 53 publications

(68 citation statements)

References 95 publications

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“…The latter indicates that eosinophils may indirectly contribute to the control of neutrophil-induced inflammation, preventing the consequences of exacerbated inflammation in those patients who recovered. This makes sense because, although the role of eosinophils in inflammation remains controversial, numerous studies in animal models and in humans have collectively indicated that eosinophils have several different functional roles, exerting proinflammatory, inhibitory, and/or regulatory effects at inflamed sites due, in part, to the existence of distinct eosinophil subpopulations in the same tissue [ 52 ]. Specifically, regarding the role of eosinophils in resolving inflammation, it has been observed in murines that eosinophils are recruited to the inflamed loci during the resolution phase, where they locally produce anti-inflammatory and pro-resolving lipid mediators, such as protectin D1 and resolvin E3, through a 12/15-lipooxygenase-mediated biosynthetic route.…”

Section: Discussionmentioning

confidence: 99%

Behavior of Eosinophil Counts in Recovered and Deceased COVID-19 Patients over the Course of the Disease

Cortés-Vieyra

Gutiérrez-Castellanos

Álvarez-Aguilar

et al. 2021

Viruses

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Knowledge about the immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, particularly regarding the function of eosinophils, has been steadily emerging recently. There exists controversy regarding the implications of eosinophils in the coronavirus disease 2019 (COVID-19)’s pathology. We report a retrospective cohort study including the comparison of leukocyte counts in COVID-19 patients, considering the outcomes of recovery (n = 59) and death (n = 60). Among the different types of leukocytes, the eosinophil counts were those that showed the greatest difference between recovered and deceased patients. Eosinopenia (eosinophil count < 0.01 × 109/L) was more frequently observed in deceased than recovered patients (p = 0.0012). The eosinophil counts more rapidly increased and showed a greater proportion over the course of the disease in the recovered than deceased patients. Furthermore, the estimated survival rate was greater in patients without eosinopenia than in patients with eosinopenia (p = 0.0070) during hospitalization. Importantly, recovered but not deceased patients showed high negative correlations of the eosinophils with the neutrophil-to-lymphocyte ratio (NLR) and neutrophil counts at Day 9 of the onset of clinical symptoms (p ≤ 0.0220). Our analysis suggests that eosinopenia may be associated with unfavorable disease outcomes and that the eosinophils have a beneficial function in COVID-19 patients, probably contributing by controlling the exacerbated inflammation induced by neutrophils.

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Section: Discussionmentioning

confidence: 99%

Behavior of Eosinophil Counts in Recovered and Deceased COVID-19 Patients over the Course of the Disease

Cortés-Vieyra

Gutiérrez-Castellanos

Álvarez-Aguilar

et al. 2021

Viruses

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“…An analysis of eosinophil subpopulations could be useful to clarify the activity of these cells in the presence of a tumor. In fact, eosinophils are cells involved in numerous physiological and pathological processes, suggesting that the behavior of eosinophils in different situations depends on specific cell characteristics [ 91 ]. Historically, eosinophils were classified into hypodense and normodense, with the former having a greater cytotoxic capacity [ 92 ].…”

Section: Discussionmentioning

confidence: 99%

“…More recently, eosinophils have been divided into resident and inducible based on the expression of several phenotypic markers such as CD45, sialic acid-binding immunoglobulin-like lectin (Siglec) F (Siglec-F) for mice or 8 (Siglec-8) for human, IL-5 receptor alpha (IL-5Rα), CD11b, and CCR3 [ 93 ]. In particular, resident eosinophils show inhibitory activity of the immune system and are comparable to normodense eosinophils, while inducible eosinophils have a proinflammatory activity and are comparable to hypodense eosinophils [ 91 ]. Studies published by Johansonn and Metcalfe showed that several activation markers are more highly expressed by circulating eosinophils in allergic subjects [ 94 , 95 ].…”

Section: Discussionmentioning

confidence: 99%

Immunity and Breast Cancer: Focus on Eosinophils

Poncin¹,

Onesti

Josse

et al. 2021

Biomedicines

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The role of eosinophils, a cell type involved in the immune response to parasitic infections and allergies, has been investigated in different cancer types, in both tumor tissue and at the circulating level. Most studies showed a role mainly in conjunction with immunotherapy in melanomas and lung tumors, while few data are available in breast cancer. In this review, we summarize literature data on breast cancer, showing a prognostic role of circulating eosinophil counts as well as of the presence of tumor tissue infiltration by eosinophils. In particular, some studies showed an association between a higher circulating eosinophil count and a good prognosis, as well as an association with response to neoadjuvant chemotherapy in hormone receptor-negative/HER2-positive and in triple negative breast cancer. Several mechanistic studies have also been conducted in in vivo models, but the exact mechanism by which eosinophils act in the presence of breast cancer is still unknown. Further studies on this subject are desirable, in order to understand their role at the cellular level, identify related biomarkers and/or possibly search for new therapeutic targets.

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“…On the basis of differences in surface expression markers, blood and tissue rEOS specifically express the surface molecule L-selectin, also known as CD62L [ 3 ]. Furthermore, on the basis of differences in granularity-related eosinophil subtype density, rEOS and iEOS were characterized by normodense and hypodense eosinophils, respectively [ 22 ]. Moreover, blood rEOS-like cells in inflammation conditions in the presence of pro-inflammatory mediators can demonstrate distinct functions compared to those in steady-state.…”

Section: Discussionmentioning

confidence: 99%

“…The inclusion of rEOS-like cells demonstrated a greater effect on ASM cell proliferation compared to iEOS-like cells in all the investigated groups. The enhanced activity of rEOS-like cells on ASM cell proliferation may be related to overexpressed homeostatic rEOS functions; rEOS showed remarkable ability for tissue repair and regeneration [ 22 ]; therefore, the constant attempt to ensure the stable regeneration of structural cells during asthma conditions may be associated with impaired pro-proliferative function. Lastly, rEOS could be associated with IL-4-driven regenerative responses to tissue injury [ 34 , 35 ] and with initiating efficient airway tissue regeneration involving the activation and proliferation of ASM cells.…”

Section: Discussionmentioning

confidence: 99%

α4β1 and αMβ2 Integrin Expression and Pro-Proliferative Properties of Eosinophil Subtypes in Asthma

Jurkevičiūtė

Januškevičius

Rimkūnas

et al. 2021

JPM

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Eosinophilic inflammation is one of the main pathophysiological features in asthma. Two subtypes of eosinophils exist in the lung and systemic circulation: lung-resident eosinophils (rEOS) and inflammatory eosinophils (iEOS). We evaluated the expression of α4β1 and αMβ2 integrins of eosinophil subtypes and their influence on airway smooth muscle (ASM) cell proliferation and viability in asthma. We included 16 severe non-allergic eosinophilic asthma (SNEA) patients, 13 steroid-free, non-severe allergic asthma (AA) patients, and 12 healthy control subjects (HS). For AA patients, a bronchial allergen challenge with Dermatophagoides pteronyssinus was performed. The eosinophil subtypes were distinguished using magnetic bead-labeled antibodies against surface CD62L, and individual combined cell cultures were prepared with ASM cells. The integrins gene expression was analyzed by a quantitative real-time polymerase chain reaction. Proliferation was assessed by the Alamar blue assay, and viability by annexin V and propidium iodide staining. rEOS-like cells were characterized by the relatively higher gene expression of the β1 integrin subunit, whereas iEOS-like cells were characterized by the αM and β2 integrin subunits. The inclusion of either eosinophil subtypes in co-culture significantly increased the proliferation of ASM cells, and the effect of rEOS-like cells was stronger than iEOS-like cells (p < 0.05). Furthermore, rEOS-like cells had a more pronounced effect on reducing ASM cell apoptosis compared to that of iEOS-like cells (p < 0.05). Lastly, the bronchial allergen challenge significantly enhanced only the iEOS-like cells’ effect on ASM cell proliferation and viability in AA patients (p < 0.05). These findings highlight the different expression of α4β1 and αMβ2 integrins on distinct eosinophil subtypes in asthma. Therefore, rEOS-like cells have a stronger effect in stimulating ASM cell proliferation and viability; however, contact with specific allergens mainly enhances pro-proliferative iEOS-like cell properties.

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The multiple functions and subpopulations of eosinophils in tissues under steady-state and pathological conditions

Cited by 53 publications

References 95 publications

Behavior of Eosinophil Counts in Recovered and Deceased COVID-19 Patients over the Course of the Disease

Behavior of Eosinophil Counts in Recovered and Deceased COVID-19 Patients over the Course of the Disease

Immunity and Breast Cancer: Focus on Eosinophils

α4β1 and αMβ2 Integrin Expression and Pro-Proliferative Properties of Eosinophil Subtypes in Asthma

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