变应原诱导常年性变应性鼻炎患者血液中CCR3+粒细胞亚群活化

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Abstract:Objective Toexplore theeffectsofallergensonactivationof blood CCR3* granulocyte subtypesinpatientswith alergic rhinitis (AR).MethodsFlowcytometrywasusedtoexaminetheeffctsof allrgensonCD63and CD203cexpressions on CCR3+CD203ceosinophilsand CCR3+CD203c+ basophilsof AR patients. Plasmalevelsof IL-25and TSLP of the patients weredetectedwithmultipleximmunoassayndELSAespectivelyandtherorrelationswithosinopilsandbsohils wereanalyzed.RNA-sequencing ofbloodCD16granulocytesfromARpatients wasperformed,andenrichmentanalysis was usedtoexplorethefunctionsandpotentialmechanismsofthediferentiallyexpressedgenes.ResultsThepercentagesof eosinophilsand basophils in CCR3+ granulocytes increased significantly in AR patients (P<0.005) ,andexposure to allergens further upregulated the percentage of basophils (P<0.005) . CD63 expression was significantly increased in patients with seasonal AR(sAR) and perennialAR (pAR) (P<0.005) butnotinAR patients negative forskinpricktest (nAR).Allergen exposures enhanced the expressons of CD63 and CD203c on eosinophils and basophils in pAR patients (P<0.005) .Elevated plasma IL-25 and TSLP levels in AR patients were associated with increased eosinophil and basophil counts (P<0.005) . The 3999 differentially expressed genes in CD16 granulocytesfrom AR patients positiveforskin prick test (SPT)were involved in protein synthesis,energy metabolismand immune functionand inendocytosis,phagosome andcarbon metabolism pathways. Conclusion The findingsin this study enrich the understanding of the roles of CCR3+ eosinophilsand basophils in the pathogenesis of SPT+AR and reveal potential therapeutic targets for AR.
Keywords: allergen; allergic rhinitis; basophils; eosinophil; activation
变应性鼻炎(AR)是一种常见的多种免疫细胞和细胞因子参与的病理机制复杂的过敏性疾病,其中IgE介导的免疫反应在AR发病中起重要作用:个体首次吸入变应原可诱导浆细胞产生特异性IgE,IgE随后与嗜碱性粒细胞和肥大细胞表面的高亲和力IgE受体Iα链(FcεRIα)结合;再次暴露于相同变应原时,变应原与IgE结合,诱导嗜碱性粒细胞和肥大细胞脱颗粒,释放组胺、白三烯等炎症介质,进而诱导过敏的急性症状。(剩余15835字)