Niranjan Rituraj, Rajavelu Priya, Ventateshaiah Sathisha Upparahalli, Shukla Jai Shankar, Zaidi Asifa, Mariswamy Siddesha Jalahalli, Mattner Jochen, Fortgang Ilana, Kowalczyk Monika, Balart Luis, Shukla Anshi, Mishra Anil
Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Section of Pulmonary Diseases, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Clin Immunol. 2015 Apr;157(2):103-13. doi: 10.1016/j.clim.2015.01.007. Epub 2015 Jan 28.
IL-18 is induced in food allergy and EoE is food allergen-induced disease. Therefore, we tested the hypothesis whether IL-18 is involved in food allergen-induced EoE pathogenesis. Accordingly, we examined normal SPT+ and SPT- EoE patient blood and biopsy samples for IL-18, IL-18Rα, ICAM and VCAM expression. Herein, we show increased IL-18 level is highly significant in food allergen SPT+ compared to SPT- EoE patients. We also report that IL-18Rα+ cells and mRNA levels are induced in the esophageal biopsies of EoE patients and blood IL-18 levels correlate with esophageal eosinophilia (P<0.01). Additionally, we report that the levels of esophageal eosinophil and mast cells correlate with ICAM expression in human EoE. Mechanistically, we show that IL-18 in vitro stimulates iNKT cells and endothelial cells and induce eosinophil active cytokines IL-5 and IL-13. We provide the evidence that IL-18 is critical cytokine involved in activation of iNKT cells and ICAM in promoting human EoE.
白细胞介素-18在食物过敏中被诱导产生，而嗜酸性食管炎是食物过敏原诱导的疾病。因此，我们检验了白细胞介素-18是否参与食物过敏原诱导的嗜酸性食管炎发病机制这一假设。相应地，我们检测了正常速发型皮肤试验阳性（SPT+）和速发型皮肤试验阴性（SPT-）的嗜酸性食管炎患者血液及活检样本中白细胞介素-18、白细胞介素-18受体α、细胞间黏附分子（ICAM）和血管细胞黏附分子（VCAM）的表达。在此，我们发现与SPT-的嗜酸性食管炎患者相比，食物过敏原SPT+患者体内白细胞介素-18水平显著升高。我们还报告称，嗜酸性食管炎患者的食管活检组织中白细胞介素-18受体α+细胞及mRNA水平升高，且血液中白细胞介素-18水平与食管嗜酸性粒细胞增多相关（P<0.01）。此外，我们报告称，在人类嗜酸性食管炎中，食管嗜酸性粒细胞和肥大细胞的水平与ICAM表达相关。从机制上来说，我们发现白细胞介素-18在体外可刺激不变自然杀伤T细胞（iNKT细胞）和内皮细胞，并诱导嗜酸性粒细胞活性细胞因子白细胞介素-5和白细胞介素-13产生。我们提供的证据表明，白细胞介素-18是参与激活iNKT细胞和ICAM以促进人类嗜酸性食管炎发生的关键细胞因子。
