Maskey Anish, Srivastava Kamal, Soffer Gary, Dunkin David, Yuan Qian, Li Xiu-Min
Department of Pathology, Microbiology & Immunology, New York Medical College, Valhalla, NY, USA.
General Nutraceutical Technology, LLC, Elmsford, NY, USA.
J Inflamm Res. 2022 Sep 23;15:5527-5540. doi: 10.2147/JIR.S372449. eCollection 2022.
Eosinophilic Esophagitis (EoE) is an increasingly common chronic inflammatory disease. The pathological mechanisms underlying EoE are largely unknown.
We sought to understand the mechanisms underlying aeroallergen-induced EoE in Sharpin gene deficient (Sharpin-/-) mice that is prone to inflammatory response.
Sharpin-/-mice were exposed with and ovalbumin intranasally every alternate day for 4 weeks. Wild type (WT) naïve mice, WT exposed, and un-exposed Sharpin-/- mice were controls. Histopathological analysis was performed by H&E, trichrome and major basic protein staining. Total and specific IgE, IgG, and IgA levels were measured by ELISA and Th2 cytokine and CCL11 chemokine gene expression were determined.
Airborne allergen exposed Sharpin-/- mice showed severe eosinophilic inflammation in the esophagus (p < 0.001), and markedly increased epithelial thickening (p < 0.0001) compared to WT normal controls, whereas airborne allergen exposed WT mice and unexposed Sharpin-/- mice only showed mild eosinophilic inflammation in the esophagus. These exposed Sharpin-/- mice also showed over 7-fold increase in blood eosinophils (p < 0.0001), 60-fold increase in eosinophils in bronchoalveolar lavage fluid (p < 0.0001) and 4-fold increase in eosinophils in the skin (p < 0.0001) compared to normal controls. Surprisingly, exposed Sharpin-/- mice did not show elevation of serum total or antigen-specific IgE levels but reduced total IgA and IgG levels than normal controls There was a marked increase in IL-4, IL-13 and CCL11 gene expression in esophageal tissue (p < 0.001) in exposed Sharpin-/- mice compared to WT normal mice.
Th2 cytokines and chemokines, but not IgE may play an important pathologic role in aeroallergen-induced EoE. This study may provide insight into new therapeutics for EoE.
嗜酸性粒细胞性食管炎（EoE）是一种日益常见的慢性炎症性疾病。EoE的病理机制在很大程度上尚不清楚。
我们试图了解在易发生炎症反应的Sharpin基因缺陷（Sharpin-/-）小鼠中，空气变应原诱导的EoE的潜在机制。
每隔一天给Sharpin-/-小鼠鼻内注射和卵清蛋白，持续4周。野生型（WT）未致敏小鼠、WT暴露小鼠和未暴露的Sharpin-/-小鼠作为对照。通过苏木精-伊红（H&E）、三色染色和主要碱性蛋白染色进行组织病理学分析。通过酶联免疫吸附测定（ELISA）测量总IgE、特异性IgE、IgG和IgA水平，并测定Th2细胞因子和CCL11趋化因子基因表达。
与WT正常对照相比，暴露于空气传播变应原的Sharpin-/-小鼠食管出现严重的嗜酸性粒细胞炎症（p < 0.001），上皮增厚明显增加（p < 0.0001），而暴露于空气传播变应原的WT小鼠和未暴露的Sharpin-/-小鼠食管仅出现轻度嗜酸性粒细胞炎症。与正常对照相比，这些暴露的Sharpin-/-小鼠血液嗜酸性粒细胞增加超过7倍（p < 0.
