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Phenomics 2024年第1期4卷 46-50页

作者： Zhenwei Tang Guowei Zhou Yi Xiao Hong Liu Xiang Chen Minxue Shen Department of Dermatology Xiangya HospitalCentralSouth University110 Xiangya RoadChangsha 410008HunanChina Hunan Key Laboratory of Skin Cancer and Psoriasis HunanEngineering Research Center of Skin Health and DiseaseCentral South UniversityChangsha 410008HunanChina Department of Dermatology Second AfliatedHospitalZhejiang University School of MedicineHangzhou 310009ZhejiangChina Furong Laboratory Changsha 410008HunanChina Department of Social Medicine and Health Management Xiangya School of Public HealthCentral South UniversityChangsha 410008HunanChina

Commonly afected in early-life population,the impact of allergic phenotypes on mid-or late-life health is less discussed.This study is to explore the association of allergic phenotypes including atopic dermatitis(AD),asthma,eosinophils count(EC),and sarcopenia.We conducted observational studies and mendelian randomization(MR)analysis based on UK Biobank(UKB),the China Health and Retirement Longitudinal Study(CHARLS)and data from genome-wide association study(GWAS).Based on the UKB data,AD,asthma and EC were positively correlated with pre-sarcopenia and decreased skeletal muscle mass index and hand grip in fully adjusted model.Asthma and EC were signifcantly associated with sarcopenia while AD was marginally associated(p=0.095).Based on the CHARLS cohort,asthma signifcantly added 109.4%risk for pre-sarcopenia in adjusted model(relative risk=2.094;p=0.002),respectively.Both asthma(β=0.100,p=0.006)and EC(β=0.023,p=0.017)exerted signifcantly casual efects on pre-sarcopenia.However,as for sarcopenia,merely EC exhibited a signifcantly casual efect(β=0.005,p=0.048).Signifcant casual efects of AD(β=–0.027,p=0.003),asthma(β=–0.029,p=0.027)and EC(β=–0.041,p<0.001)on decreased appendicular lean mass(ALM)were observed using the inverse-variance weighted method and the Mendelian randomization pleiotropy residual sum and outlier(MR-PRESSO)method.Our results revealed a contributory role of AD,asthma and EC on sarcopenia,especially in terms of decreased ALM,an indicator for sarcopenia diagnosis.The fndings of our study will raise the awareness of preventing aging-related disorders or geriatric syndromes among allergic populations.

关键词： Sarcopenia Atopic dermatitis Asthma Aging eosinophils

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Intestinal eosinophils:characterization of elusive granulocytes as anti-bacterial and immunomodulatory effector cells in colitis

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Signal Transduction and Targeted Therapy 2023年第9期8卷 3904-3906页

作者： Tim Holland Jochen Mattner Mikrobiologisches Institut-Klinische Mikrobiologie Immunologie und HygieneUniversitätsklinikum Erlangen and Friedrich-Alexander-Universität(FAU)Erlangen-NürnbergErlangenGermany Medical Immunology Campus Erlangen FAU Erlangen-NürnbergErlangenGermany

In a recent study published in Nature,Gurtner and colleagues identify active eosinophils(A-Eos)as eosinophil subset with anti-bacterial and immune regulatory functions during intestinal disease.1 Due to the combination of human singe cell transcip-tomics with pre-clinical experimental studies,the authors suggest eosinophils as promising targets for clinical intervention in inflammatory bowel disease(IBD).eosinophils are known to exhibit versatile functions at mucosal surfaces.Thus,they can sustain the intestinal epithelial barrier as well as intestinal tissue architecture,communicate with other cell subsets and regulate local immune responses.2 However,despite having been associated with a panoply of different diseases including eosinophilic esophagitis or IBD,3 their role and plasticity in gastrointestinal disorders have not been well characterized.

关键词： eosinophils clinical diseases

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eosinophils in the gastrointestinal tract and their role in the pathogenesis of major colorectal disorders

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World Journal of Gastroenterology 2019年第27期25卷 3503-3526页

作者： Alexandre Loktionov DiagNodus Ltd Babraham Research Campus

eosinophils are currently regarded as versatile mobile cells controlling and regulating multiple biological pathways and responses in health and disease.These cells store in their specific granules numerous biologically active substances(cytotoxic cationic proteins, cytokines, growth factors, chemokines,enzymes) ready for rapid release. The human gut is the main destination of eosinophils that are produced and matured in the bone marrow and then transferred to target tissues through the circulation. In health the most important functions of gut-residing eosinophils comprise their participation in the maintenance of the protective mucosal barrier and interactions with other immune cells in providing immunity to microbiota of the gut lumen. eosinophils are closely involved in the development of inflammatory bowel disease(IBD),when their cytotoxic granule proteins cause damage to host tissues. However,their roles in Crohn’s disease and ulcerative colitis appear to follow different immune response patterns. eosinophils in IBD are especially important in altering the structure and protective functions of the mucosal barrier and modulating massive neutrophil influx to the lamina propria followed by transepithelial migration to colorectal mucus. IBD-associated inflammatory process involving eosinophils then appears to expand to the mucus overlaying the internal gut surface. The author hypothesises that immune responses within colorectal mucus as well as ETosis exerted by both neutrophils and eosinophils on the both sides of the colonic epithelial barrier act as additional pathogenetic factors in IBD. Literature analysis also shows an association between elevated eosinophil levels and better colorectal cancer(CRC) prognosis, but mechanisms behind this effect remain to be elucidated. In conclusion, the author emphasises the importance of investigating colorectal mucus in IBD and CRC patients as a previously unexplored milieu of disease-related inflammatory responses.

关键词： eosinophils Eosinophilopoiesis Gut lamina propria Colorectal mucus Normal human small intestine Normal human colon Inflammatory bowel disease Crohn’s disease Ulcerative colitis Colorectal cancer

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Characteristics, phenotypes, mechanisms and management of severe asthma

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Chinese Medical Journal 2022年第10期135卷 1141-1155页

作者： Kian Fan Chung Piers Dixey Hisham Abubakar-Waziri Pankaj Bhavsari Pujan H.Patel Sujuan Guo Yang Ji National Heart&Lung Institute Imperial College LondonLondon SW36LYUK Royal Brompton&Harefield NHS Hospitals LondonUK Department of Respiratory Medicine University of Hong Kong Shenzhen HospitalShenzhenGuangdong 518053China.

Severe asthma is "asthma which requires treatment with high dose inhaled corticosteroids (ICS) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming ’’uncontrolled’ or which remains ’’uncontrolled’ despite this therapy." The state of control was defined by symptoms, exacerbations and the degree of airflow obstruction. Therefore, for the diagnosis of severe asthma, it is important to have evidence for a diagnosis of asthma with an assessment of its severity, followed by a review of comorbidities, risk factors, triggers and an assessment of whether treatment is commensurate with severity, whether the prescribed treatments have been adhered to and whether inhaled therapy has been properly administered. Phenotyping of severe asthma has been introduced with the definition of a severe eosinophilic asthma phenotype characterized by recurrent exacerbations despite being on high dose ICS and sometimes oral corticosteroids, with a high blood eosinophil count and a raised level of nitric oxide in exhaled breath. This phenotype has been associated with a Type-2 (T2) inflammatory profile with expression of interleukin (IL)-4, IL-5, and IL-13. Molecular phenotyping has also revealed non-T2 inflammatory phenotypes such as Type-1 or Type-17 driven phenotypes. Antibody treatments targeted at the T2 targets such as anti-IL5, anti-IL5Rα, and anti-IL4Rα antibodies are now available for treating severe eosinophilic asthma, in addition to anti-immunoglobulin E antibody for severe allergic asthma. No targeted treatments are currently available for non-T2 inflammatory phenotypes. Long-term azithromycin and bronchial thermoplasty may be considered. The future lies with molecular phenotyping of the airway inflammatory process to refine asthma endotypes for precision medicine.

关键词： Severe asthma Biologic therapies eosinophils Neutrophils Corticosteroid insensitivity Type 2-high inflammation

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Meteorin-β/Meteorin like/IL-41 attenuates airway inflammation in house dust mite-induced allergic asthma

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Cellular & Molecular Immunology 2022年第2期19卷 245-259页

作者： Xun Gao Ting-Fan Leung Gary Wing-Kin Wong Wing-Hung Ko Mengyun Cai Ellie Jiayi He Ida Miu-Ting Chu Miranda Sin-Man Tsang Ben Chung-Lap Chan Jiawei Ling Xiao Fan Liwei Lu Christopher Wai-Kei Lam Chun-Kwok Wong Department of Chemical Pathology The Chinese University of Hong KongHong KongChina Department of Paediatrics The Chinese University of Hong KongHong KongChina School of Biomedical Sciences The Chinese University of Hong KongHong KongChina Emory College of Arts and Sciences Emory UniversityAtlantaGAUSA Institute of Chinese Medicine and State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants The Chinese University of Hong KongHong KongChina Department of Pathology and Shenzhen Institute of Research and Innovation The University of Hong KongHong KongChina Faculty of Medicine and State Key Laboratory of Quality Research in Chinese Medicines Macao University of Science and TechnologyMacaoChina Li Dak Sum Yip Yio Chin R&D Centre for Chinese Medicine The Chinese University of Hong KongHong KongChina

We sought to examine the regulatory effect of Meteorin-β(Metrnβ)/Meteorin like(Metrnl)/IL-41 on lung inflammation in allergic asthma.We found that Metrnβwas elevated significantly in asthmatic patients and in mice with allergic asthma induced by house dust mite(HDM)extract.Upon exposure to HDM,Metrnβwas secreted predominantly by airway epithelial cells and inflammatory cells,including macrophages and eosinophils.The increased Metrnβeffectively blocked the development of airway hyperreactivity(AHR)and decreased inflammatory cell airway infiltration and type 2 cytokine production,which was associated with downregulated DC-mediated adaptive immune responses.Moreover,Metrnβimpaired the maturation and function of bone marrow-derived dendritic cells in vitro.Asthmatic mice adoptively transferred with dendritic cells isolated from Metrnβ-treated allergic mice displayed decreased AHR,airway inflammation,and lung injury.Metrnβalso displayed anti-inflammatory properties in immunodeficient SCID mice with allergic asthma and in in vitro 3D ALI airway models.Moreover,blockade of Metrnβby anti-Metrnβantibody treatment promoted the development of allergic asthma.These results revealed the unappreciated protective roles of Metrnβin alleviating DC-mediated Th2 inflammation in allergic asthma,providing the novel treatment strategy of therapeutic targeting of Metrnβin allergic asthma.

关键词： Metrnβ eosinophils Dendritic cells Allergic asthma Air-liquid interface

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Neutrophil membrane-camouflaged nanoparticles alleviate inflammation and promote angiogenesis in ischemic myocardial injury

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Bioactive Materials 2023年第5期23卷 369-382页

作者： Dongjian Han Fuhang Wang Zhentao Qiao Bo Wang Yi Zhang Qingjiao Jiang Miaomiao Liu Yuansong Zhuang Quanxu An Yan Bai Jiahong Shangguan Jinying Zhang Gaofeng Liang Deliang Shen Department of Cardiology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou450000China Key Laboratory of Cardiac Injury and Repair of Henan Province ZhengzhouChina Department of Vascular and Endovascular Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou450000China School of Basic Medical Sciences Henan University of Science and TechnologyLuoyang471023HenanChina

Acute myocardial infarction(AMI)induces a sterile inflammatory response,leading to cardiomyocyte damage and adverse cardiac remodeling.Interleukin-5(IL-5)plays an essential role in developing eosinophils(EOS),which are beneficial for the resolution of inflammation.Furthermore,the proangiogenic properties of IL-5 also contribute to tissue healing following injury.Therefore,targeted delivery of IL-5 is an innovative therapeutic approach for treating AMI.It has been shown that conventional IL-5 delivery can result in undesirable adverse effects and potential drug overdose.In this study,we successfully synthesized a biomimetic IL-5 nanoparticle by camouflaging the IL-5 nanoparticle in a neutrophilic membrane.The administration of neutrophil membrane-camouflaged nanoparticles(NM-NPIL-5)in the in vivo model showed that these nanoparticles promoted EOS accumulation and angiogenesis in the infarcted myocardium,thereby limiting adverse cardiac remodeling after AMI.Our results also demonstrated that the NM-NPIL-5 could serve as neutrophil“decoys”to adsorb and neutralize the elevated neutrophil-related cytokines in the injured heart by inheriting multiple receptors from their“parent”neutrophils.Finally,the targeted delivery of NM-NPIL-5 protected the cardiomyocytes from excessive inflammatory-induced apoptosis and maintained cardiac function.Our findings provided a promising cardiac detoxification agent for acute cardiac injury.

关键词： Biomimetic nanoparticles Interleukin-5 eosinophils Angiogenesis Myocardial infarction

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Blood eosinophils and mortality in patients with acute respiratory distress syndrome: A propensity score matching analysis

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World Journal of Emergency Medicine 2021年第2期12卷 131-136页

作者： Hao-tian Chen Jian-feng Xu Xiao-xia Huang Ni-ya Zhou Yong-kui Wang Yue Mao Department of Emergency Intensive Care Unit the Second Affi liated Hospital of Zhejiang University School of MedicineHangzhou 310009China Department of Respiratory Therapy the Second Affi liated Hospital of Zhejiang University School of MedicineHangzhou 310009China Department of Respiratory Medicine the Second Affi liated Hospital of Zhejiang University School of MedicineHangzhou 310009China Department of Medical Administration the Second Affi liated Hospital of Zhejiang University School of MedicineHangzhou 310009China Department of Cardiology the Second Affi liated Hospital of Zhejiang University School of MedicineHangzhou 310009China

BACKGROUND: The effect of blood eosinophils(EOSs) on mortality in acute respiratory distress syndrome(ARDS) patients and whether corticosteroids affect this effect are unclear.METHODS: The Medical Information Mart for Intensive Care III database(version 1.4) was used to extract data. Patients with ARDS were selected for inclusion. Cox regression models using the backward stepwise method and propensity score matching(PSM) were used to assess the relationship between blood EOS counts and 28-day mortality. RESULTS: A total of 2,567 patients with ARDS were included, and the 28-day mortality rate was 24.19%. The crude 28-day mortality was significantly lower in patients with EOS counts ≥2%(18.60% [85/457] vs. 25.40% [536/2,110], P=0.002) than in those with EOS counts <2%. In the Cox regression model, the EOS counts ≥2% showed a significant association with the decreased 28-day mortality(hazard ratio [HR] 0.731;95% confidence interval [95% CI] 0.581–0.921, P=0.008). In the corticosteroid non-use subgroup, EOS counts ≥2% was significantly related to decreased 28-day mortality(HR 0.697, 95% CI 0.535–0.909, P=0.008), but the result was not significant in the corticosteroid non-use subgroup model(P=0.860). A total of 457 well-matched pairs were obtained by a 1:1 matching algorithm after PSM. The 28-day mortality remained significantly lower in the EOS counts ≥2% group(18.60% [85/457] vs. 26.70% [122/457], P=0.003).CONCLUSIONS Higher EOS counts are related to lower 28-day mortality in ARDS patients, and this relationship can be counteracted by using corticosteroids.

关键词： Critical care Acute respiratory distress syndrome eosinophils Mortality Corticosteroid

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Intracellular signaling mechanisms regulating the activation of human eosinophils by the novel Th2 cytokine IL-33:implications for allergic inflammation

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Cellular & Molecular Immunology 2010年第1期7卷 26-34页

作者： Joyce YS Chow Chun K Wong Phyllis FY Cheung Christopher WK Lam Department of Chemical Pathology The Chinese University of Hong KongPrince of Wales HospitalShatinNTHong KongChina Macao Institute for Applied Research in Medicine and Health Macao University of Science and Technology FoundationMacaoChina

The novel interleukin(IL)-1 family cytokine IL-33 has been shown to activate T helper 2(Th2)lymphocytes,mast cells and basophils to produce an array of proinflammatory cytokines,as well as to mediate blood eosinophilia,IgE secretion and hypertrophy of airway epithelium in mice.In the present study,we characterized the activation of human eosinophils by IL-33,and investigated the underlying intracellular signaling mechanisms.IL-33 markedly enhanced eosinophil survival and upregulated cell surface expression of the adhesion molecule intercellular adhesion molecule(ICAM)-1 on eosinophils,but it suppressed that of ICAM-3 and L-selectin.In addition,IL-33 mediates significant release of the proinflammatory cytokine IL-6 and the chemokines CXCL8 and CCL2.We found that IL33-mediated enhancement of survival,induction of adhesion molecules,and release of cytokines and chemokines were differentially regulated by activation of the nuclear factor(NF)-KB,p38 mitogen-activated protein kinase(MAPK)and extracellular signal-regulated kinase(ERK)pathways.Furthermore,we compared the above IL-33 activities with two structurally and functionally related cytokines,IL-1 B and IL-18.IL-1β,but not IL-18,markedly upregulated cell surface expression of ICAM-1.IL-1βand IL-18 also significantly enhanced eosinophil survival,and induced the release of IL-6 and chemokines CXCL8 and CCL2 via the activation of the NF-κB,p38 MAPK and ERK pathways.Synergistic efects on the release of IL-6 were also observed in combined treatment withIL-1B,IL-18 and IL-33.Taken together,our findings provide insight into IL-33-mediated activation of eosinophils via differential intracellular signaling cascades in the immunopathogenesis of allergic inflammation.

关键词： allergy cytokines eosinophils signal transduction

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NOD-like receptors mediated activation of eosinophils interacting with bronchial epithelial cells： a link between innate immunity and allergic asthma

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Cellular & Molecular Immunology 2013年第4期10卷 317-329页

作者： Churl Kwok Wong Shuiqing Hu Karen Ming-Lam Leungt Jie Dong Lan He Yi Jun Chu Ida Miu-Ting Chu Huai-Na Qiu Kelly Yan-Ping Liu ChristopherWai-Kei Lam Department of Chemical Pathology The Chinese University of Hong Kong Prince of Wales Hospital Hong Kong China Department of Medicine and Therapeutics The Chinese University of Hong Kong Prince of Wales Hospital Hong Kong China Macao Institute for Applied Research in Medicine and Health Macao University of Science and Technology Taipa Macao China

Key intracytosolic pattern recognition receptors of innate immunity against bacterial infections are nucleotide-binding oligomerization domain （NOD）-Iike receptors （NLRs）. We elucidated the NOD1 and NOD2-mediated activation of human eosinophils, the principal effector cells for allergic inflammation, upon interacting with human bronchial epithelial BEAS-2B cells in allergic asthma. eosinophils constitutively expressed NOD1,2 but exhibited nonsignificant responses to release chemokines upon the stimulation by NOD1 ligand 7-D-glutamyl-meso-diaminopimelic acid （iE-DAP） and NOD2 ligand muramyl dipeptide （MDP）. However, iE-DAP and MDP could significantly upregulate cell surface expression of CD18 and intercellular adhesion molecule （ICAM）-I on eosinophils and ICAM-1 on BEAS-2B cells, as well as induce chemokines CCL2 and CXCL8 release in the coculture system （all P〈0.05）. Both eosinophils and BEAS-2B cells were the main source for CXCL8 and CCL2 release in the coculture system upon iE-DAP or MDP stimulation. Direct interaction between eosinophils and BEAS-2B cells is responsible for CCL2 release, and soluble mediators are implicated in CXCL8 release. ERK and NF-KB play regulatory roles for the expression of adhesion molecules and chemokines in coculture. Treatment with NOD1,2 ligand could induce the subepithelial fibrosis and significantly enhance the serum concentration of total IgE, chemokine CCL5 for eosinophils and T helper type 2 （Th2） cells and asthma Th2 cytokine IL-13 in bronchoalveolar lavage fluid of ovalbumin-sensitized allergic asthmatic mice （all P〈0.05）. This study provides further evidence of bacterial infection-mediated activation of NOD1,2 in triggering allergic asthma via the activation of eosinophils interacting with bronchial epithelial cells at inflammatory airway.

关键词： allergy bronchial epithelial cells chemokines eosinophils signal transduction

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Protein kinase C in proliferation and infiltration of eosinophils in nasal polyp

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Chinese Medical Journal 2003年第10期116卷 1553-1556页

作者：李美华董震杨占泉白蕴红 Department of ORP-HNS China-Japan Union HospitalJilin University Department of Neuroscience Dentistry of New Jersey University of Medicine

Objective To explore the significance of protein kinase C (PKC) in proliferation and infiltration of eosinophils in nasal polyps. Methods With in situ hybridization and immunohistochemistry staining methods,PKC,pro-apoptotic,and anti-apoptotic gene (Bax,bcl-2 ) expressions were measured in nasal polyp tissues from 26 patients and inferior turbinate mucosa tissues (ITMTs) from 20 healthy persons. The May-Grünwald-Giemsa (MGG) staining method was used to identify eosinophils. Results In eosinophils,the positive cell expressive rates of Bcl-2 mRNA and its protein were significantly higher in the group with nasal polyps than in the ITMT group ( P 0.05). There was PKC expression in the eosinophils of 26 cases of nasal polyps,but occasional PKC expression in 7 of 20 ITMT cases. In the two groups,PKC positive cell expression was significantly different,and the expression of PKC and bcl-2 mRNA as well as associated protein in eosinophils of nasal polyps showed a remarkably positive relationship ( r 1=0.0875,r 2=0.0823,P eosinophils of nasal polyp tissues is closely associated with apoptosis inhibition,and it is presumed that eosinophil apoptosis inhibition in nasal polyp tissues is obtained by activation of the PKC signal transduction pathway.

关键词： protein kinase C nasal polyp eosinophils in situ hybridization immunohistochemistry

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