The emerging roles of eosinophils: Implications for the targeted treatment of eosinophilic-associated inflammatory conditions

Lombardi, Carlo; Berti, Alvise; Cottini, Marcello

doi:10.1016/j.crimmu.2022.03.002

Cited by 60 publications

(73 citation statements)

References 121 publications

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“…Neutralizing antibodies directed against IL-5 (α–IL-5) treatment did not impact the numbers of rEOS but substantially inhibited the recruitment of iEOS in the mice’s lungs. Anti-IL5 for KD patients with an iEOS phenotype or in KD patients with prognostic biomarkers of future allergic diseases would be considered [ 46 ]. An area of future research that should be considered is prognostic and therapeutic biomarkers of long-term allergic complications, the influence on acute treatment, and the strategy for preventing them.…”

Section: Discussionmentioning

confidence: 99%

Expression of Eosinophilic Subtype Markers in Patients with Kawasaki Disease

Chang

Chen

Huang

et al. 2022

IJMS

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Purpose: Eosinophils may rise to a higher level in the acute phase of Kawasaki disease (KD) both before and after intravenous immunoglobulin (IVIG) therapy. A substantial body of research was carried out on the association between KD and allergic diseases. Eosinophils play an important role in type 2 inflammation. Recent studies have shown that there are two distinct subtypes of eosinophils. In addition to their role in inflammation, lung-resident eosinophils (rEOS) also regulate homeostasis. Inflammatory eosinophils (iEOS) reflect type 2 inflammation in tissues. iEOS were considered the primary eosinophils in non-severe allergic asthma, while rEOS were thought to be the primary eosinophils in severe non-allergic eosinophilic asthma. This case–control study aimed to investigate the marker expression of eosinophilic subtypes in KD patients. Materials and Methods: The marker expressions of eosinophilic subtypes in the leukocytes of patients with KD were evaluated by the recently established KDmarkers online tool, a web server including gene expression data. Finally, the results were validated with a quantitative reverse transcriptase polymerase chain reaction (RT-PCR). We analyzed the mRNA expression levels of SELL and IL10RA in leukocytes from KD patients and febrile children. Results: Included in our screening tools were transcriptome arrays, which provided clues showing the importance of rEOS, whose role was identified by three genes (lower IL10RA, higher SELL, and SERPINB1 than controls). In contrast, the iEOS representative gene CD101 was not elevated in KD. It was found that the gene IL10RA, a marker of inflammatory eosinophilic leukocytes, was more highly expressed in the leukocytes of KD patients (n = 43) than febrile controls (n = 32), especially those without coronary artery lesions (CAL) (n = 26). Before treatment, SELL expression was higher in leukocytes of CAL patients (CAL, 1.33 ± 0.18, n = 39; non-CAL, 0.87 ± 0.12, n = 55; p = 0.012). SELL was significantly higher after half a year compared to febrile controls. Conclusions: To our knowledge, this is the first study to demonstrate that KD patients have increased SELL than febrile controls after 6 months of treatment. We present evidence here that dynamically different eosinophilic involvement exists between KD patients with and without CAL. The role of eosinophilic subtypes in KD patients warrants further investigation.

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Section: Discussionmentioning

confidence: 99%

Expression of Eosinophilic Subtype Markers in Patients with Kawasaki Disease

Chang

Chen

Huang

et al. 2022

IJMS

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“…Activation of eosinophils and subsequent release of eosinophilic mediators (mainly cytokines and type 2 chemokines) are potent pro-inflammatory effectors [ 80 ] and a significant association has been established between eosinophilia and some systemic inflammatory diseases [ 81 ]. The involvement of eosinophilia in inflammatory pathologies of the gastrointestinal, vascular, locomotor, and in general of the various mucous surfaces of the organism is known in the literature, and of course, eosinophils play key role in the pathogenesis of both upper and lower airway inflammation, with a spectrum of pathologic manifestations ranging from allergic rhinitis with or without nasal polyposis to asthma, and even allergic bronchopulmonary aspergillosis [ 82 ].…”

Section: Eosinophil Structure and Biologymentioning

confidence: 99%

Eosinophilic inflammation: An Appealing Target for Pharmacologic Treatments in Severe Asthma

et al. 2022

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Severe asthma is characterized by different endotypes driven by complex pathologic mechanisms. In most patients with both allergic and non-allergic asthma, predominant eosinophilic airway inflammation is present. Given the central role of eosinophilic inflammation in the pathophysiology of most cases of severe asthma and considering that severe eosinophilic asthmatic patients respond partially or poorly to corticosteroids, in recent years, research has focused on the development of targeted anti-eosinophil biological therapies; this review will focus on the unique and particular biology of the eosinophil, as well as on the current knowledge about the pathobiology of eosinophilic inflammation in asthmatic airways. Finally, current and prospective anti-eosinophil therapeutic strategies will be discussed, examining the reason why eosinophilic inflammation represents an appealing target for the pharmacological treatment of patients with severe asthma.

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“…As FeNO can reflect the characteristics of the inflammatory profile and whether T2 inflammation may be present, it could be helpful in the selection of biologics for severe asthma ( 28 , 41 , 42 ).…”

Section: Introductionmentioning

confidence: 99%

What is the added value of FeNO as T2 biomarker?

Marcos

Serrano

2022

Front. Allergy

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There is increasing evidence about the role of nitric oxide in type 2 (T2) immune response. Fraction of exhaled nitric oxide (FeNO) is a product of airways inflammation and it is increased in patients with asthma. Since Gustaffson published the first article about this biomarker in the 1990s, interest has continued to grow. Compared with other T2 biomarkers such as blood eosinophil count, induced sputum, or serum periostin, FeNO has some remarkable advantages, including its not invasive nature, easy repeatability, and possibility to be performed even in patients with severe airway obstruction. It is considered as an indicator of T2 inflammation and, by the same token, a useful predictor for inhaled steroid response. It is difficult to determine the utility of nitric oxide (NO) for initial asthma diagnosis. In such a heterogenous disease, a single parameter would probably not be enough to provide a complete picture. There is also an important variability among authors concerning FeNO cutoff values and the percentage of sensibility and specificity for diagnosis. Its high specificity indicates a potential role to “rule in” asthma; however, its lower sensibility could suggest a lower capacity to “rule out” this pathology. For this reason, if a diagnosis of asthma is being considered, FeNO should be considered along with other tests. FeNO has also shown its utility to detect response to steroids, adherence to treatment, and risk of exacerbation. Even though there is not enough quality of evidence to establish overall conclusions, FeNO could be an alternative procedure to diagnose or exclude asthma and also a predictive tool in asthma treated with corticosteroids.

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The emerging roles of eosinophils: Implications for the targeted treatment of eosinophilic-associated inflammatory conditions

Cited by 60 publications

References 121 publications

Expression of Eosinophilic Subtype Markers in Patients with Kawasaki Disease

Expression of Eosinophilic Subtype Markers in Patients with Kawasaki Disease

Eosinophilic inflammation: An Appealing Target for Pharmacologic Treatments in Severe Asthma

What is the added value of FeNO as T2 biomarker?

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