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Allergic rhinitis (AR) is characterized by various bothersome clinical symptoms of the nasal mucosa that impaired the quality of daily life. Different chemokine receptors play a crucial role in the recruitment of inflammatory cells in AR. However, the effect of CC chemokine receptor (CCR) 3 on the function of eosinophils (EOS) is still unclear. We investigated the effect of CCR3 on EOS in a murine model of OVA-mediated allergic rhinitis using CCR3-deficient (CCR3 -/- ) mice. In vitro, bone marrow of CCR3 -/- and wild-type (WT) mice were used to investigate the induction and development of EOS. In vivo, Allergic rhinitis was initiated in CCR3 -/- and wild-type (WT) mice by passive transfer OVA, followed by detecting the eosinophil infiltration of the nasal mucosa and bone marrow. Then CD34 + progenitor cells in bone marrow and blood were evaluated by IHC analysis. Furthermore, the degranulation proteins of EOS in nasal mucosa, marrow, blood and NALF were determined by IHC, real-time PCR analysis and Western blot. We found that CCR3 gene can regulate the growth and development of primary cultured eosinophils. Knockout CCR3 gene can inhibit the proliferation and degranulation of EOS. The infiltration of eosinophils in the nasal mucosa following OVA-challenged, was significantly higher in WT mice compared with those stimulated with phosphate-buffered saline (PBS) for WT, but that was not seen in similarly treated CCR3 -/- mice. Besides, the number of CD34 + progenitor cells in bone marrow and blood were also suppressed in CCR3 -/- mice. The degranulation proteins of EOS expressed in nasal mucosa, marrow, blood and NALF were decreased in CCR3 -/- AR mice compared with WT-AR mice. And the clinical symptoms were significantly alleviated. The expression of granulation proteins in NALF were not detected in both untreated CCR3 -/- mice and WT mice. These results demonstrate a contribution of CCR3 to both the growth, migration, and degranulation of EOS during allergic rhinitis., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This study aimed to investigate the effects of CCR3 knockdown (CCR3 -/- ) on the proliferation, migration, and degranulation of the bone marrow eosinophils (EOS) in mice. Bone marrow cells from wild-type mice (WT) were harvested for primary culture and differentiated into mature EOS, which were then randomly divided into the control, 740Y-P, and LY294002 group. The effects of different concentrations of LY294002 (PI3K inhibitor) and 740Y-P (PI3K agonist) on the proliferation viability of EOS, expressions of EPO, Akt, and p-Akt proteins, and migration changes of EOS were detected. CCR3 -/- mice were identified. Then, bone marrow cells of WT and CCR3 -/- mice were differentiated into mature EOS and grouped into WT EOS, WT EOS + eotaxin (100 ng/mL), CCR3 -/- EOS, and CCR3 -/- EOS + eotaxin (100 ng/mL) group. The changes in EOS proliferation, migration, as well as expressions of EPO, Akt, and p-Akt proteins were detected. The number of migrated cells (P < 0.01) and expression of EPO (p < 0.05) in the 740Y-P group were higher than those in the control group, while opposite trends were observed for the LY294002 group. Expression levels of p-Akt and Akt in the LY294002 group were significantly lower than in the control group (all P < 0.01). Also, the expression of p-Akt in the 740Y-P group was significantly higher than that in the control group (p < 0.05). The proliferative activity of EOS, expression of EPO and p-Akt, and the number of migrated cells in the WT EOS group were higher than those in CCR3 -/- EOS group (all P < 0.05). After adding eotaxin, the WT EOS group was higher than the other three groups (all P < 0.05). Mechanistically, CCR3 -/- inhibited EOS's proliferation, migration, and degranulation by downregulating PI3K/Akt pathway. This data suggests that the knockout of the CCR3 gene in bone marrow cells may inhibit the function of EOS by downregulating the PI3K/Akt pathway, thereby affecting AR; thus, the CCR3 gene may be a target gene for AR therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In allergic reaction activated eosinophils have been known to accumulate at the site of inflamma tion. Apoptosis of eosinophils may be involved in the inflammation resolution. In this review, we state that the apoptosis of eosinophils play a direct role in allergic reaction. Regulating the apoptosis of eosinophils can effectively alter the development of allergic inflammatory reaction.

The incidence of allergic diseases (asthma, allergic rhinitis, atopic dermatitis and food allergy) increased gradually over recent decades, and an increasing number of patients are suffering from allergic diseases, thus the rise in allergic disease incidence warrants concern. Researchers have already had a deeper understanding of the pathogenesis of allergic diseases. Mounting evidence has shown that the eosinophils play an important role in the pathogenesis of allergic diseases. Many systematic studies have been conducted about eosinophils, therefore, this review will provide a summary on recent progress in eosinophils and allergic diseases.

Objective: To explore the expression of T-bet/GATA-3 in nasal mucosa tissue of allergic rhinitis rat and to investigate the association between the expression of T-bet/GATA-3 and the eosinophil count., Method: Twenty SD rats were randomly divided into a control group and an allergic rhinitis group. The allergic rhinitis rat model was induced with ovalbumin. The total eosinophils were counted in the nasal mucosa. The concentrations of IL-4, IL-5 and IFN-gamma in nasal lavage fluid were measured by ELISA. The mRNA and protein expressions of IL-4, IL-5, IFN-gamma, T-bet and GATA-3 in the nasal mucosa were detected by RT-PCR and Western blot respectively., Result: The main inflammatory cells were eosinophils in the nasal mucosa of allergic rhinitis rats. The level of IL-4, IL-5 and IFN-gamma in control group was significantly higher than that in allergic rhinitis group (P < 0.01). The mRNA and protein expression of IFN-gamma and T-bet in allergic rhinitis group was significantly higher than that in control group (P < 0.01). While the mRNA and protein expression of IL-4, IL-5 and GATA-3 in control group was significantly higher than that in allergic rhinitis group (P < 0.01). The ratio of protein expression of T-bet and GATA-3 was negatively correlated with the eosinophil count, IL-4 and IL-5, but positively with the concentrations of IFN-gamma., Conclusion: The imbalance of transcription factor GATA-3 and T-bet has a close correlation with the eosinophil count, and may play a key role in the formation of allergic rhinitis.

The present study aimed to investigate the effects of C-C chemokine receptor type 3 (CCR3) gene knockout on allergic rhinitis (AR) in mice, as well as the underlying molecular mechanisms. Ovalbumin was administrated to CCR3+/+ and CCR3−/− BALB/c mice to establish an AR model. The mice were divided into four groups: i) Normal control (CG), ii) AR model (AR), iii) CCR3 knockout CG (CCR3−/−CG) and iv) AR model with CCR3 knockout (CCR3−/−AR). Histological sections of nasal mucosae were examined by hematoxylin and eosin staining, which revealed that CCR3 knockout suppressed the invasion of inflammatory cells and relieved the damage of nasal mucosae. Peripheral blood smear and nasal-washing smears were evaluated by Wright's staining. Eosinophil (EOS) numbers in nasal mucosae, peripheral blood, and nasal washings of the various groups were ranked in the order: AR>CCR3−/−AR>CG>CCR3−/−. mRNA expression levels of CCR3, EOS peroxidase (EPO), EOS cationic protein (ECP), and major basic protein (MBP) in the peripheral serum and nasal washings were detected by reverse transcription-polymerase chain reaction. Interferon-γ (IFN-γ), interleukin (IL)-4, IL-10, and immunoglobulin E (IgE) protein levels in the peripheral serum and nasal washings were investigated by ELISA. CCR3 mRNA expression was not detected in the CCR3−/− and CCR3−/−AR groups, whereas expression levels in the AR group were markedly higher compared with expression in the CG group. Compared with the CG-associated groups (i.e., the CG and CCR3−/−CG groups), the levels of EPO, ECP, MBP, IL-4, and IgE were significantly increased in the AR-associated groups (that is, R and CCR3−/−AR). In addition, the CCR3−/−AR group mice produced significantly lower levels of EPO, ECP, MBP, IL-4 and IgE compared with the AR group, whereas the expression levels of IFN-γ and IL-10 were increased. CCR3 gene knockout may alleviate EOS invasion and the inflammatory response in AR model mice by reducing the expression levels of EPO, ECP, MBP, IL-4, and IgE, and increasing the expression of IL-10 and IFN-γ. [ABSTRACT FROM AUTHOR]

• The OVA sensitized AR mouse model and EOL-1 cells model are established. • The level of miR-223-3p is up-regulated in AR patients and AR mice. • MiR-223-3p affects AR inflammatory response by promoting eosinophil degranulation. • FBXW7 is a target gene of miR-223-3p, and its expression is low in AR group. • MiR-223-3p affects eosinophil degranulation and AR inflammation by targeting FBXW7. MiR-223-3p is a multifunctional microRNA regulated by multiple transcription factors and plays a critical role in inflammation. This paper was designed to investigate the regulatory role and mechanism of miR-223-3p in eosinophils degranulation and allergic rhinitis (AR) inflammation. OVA sensitized AR mouse model and EOL-1 cells model were established. RT-qPCR and FISH were performed to detect the miR-223-3p expression. ELISA and WB were utilized to evaluate mRNA and protein expression. HE staining and transmission electron microscopy were applied to observe the morphological changes in nasal mucosa. Flow cytometry and immunofluorescence staining were performed to measure the proportion of eosinophils and eosinophilic major basic protein expression. The targeting relationship between miR-223-3p and FBXW7 was verified by bioinformatic analysis and dual-luciferase reporter gene assay. The expression of FBXW7 was detected by immunohistochemistry. The level of miR-223-3p in nasal mucosa was significantly up-regulated in AR group. The expression of miR-223-3p, ECP, MBP, and EPO were increased in EOL-1 cells, further increasing the miR-223-3p level could promote the ECP and EPO mRNA expression. Upregulation of miR-223-3p increased eosinophils granule protein expression, aggravated mucosal destruction and enhanced AR inflammation. Luciferase assay verified miR-223-3p directly target the 3ʹ-UTR of FBXW7. In vitro, overexpression of FBXW7 could reverse the increase in MBP expression caused by the up-regulation of miR-223-3p. In vivo, knockdown of FBXW7 could reverse the down-regulation in granule protein level caused by the down-regulation of miR-223-3p, thereby aggravating AR inflammation. Collected evidence elucidated that miR-223-3p could regulate the eosinophil degranulation and enhances the inflammation in AR by targeting FBXW7. The miR-223-3p/FBXW7 axis may provide a novel approach for AR treatment. [ABSTRACT FROM AUTHOR]