Immunopathology of the Nasal Mucosa in Sarcoidosis

描述(由申请人提供)： 呼吸道上皮通过调节粘膜炎症和组织纤维化在呼吸道和肺部疾病中发挥致病作用。结节病与上皮细胞活化和粘膜炎症有关。肉芽肿的形成通常是以支气管为中心的，某些细胞因子，如骨桥蛋白、干扰素和白细胞介素4在结节状上皮细胞中上调。这也许并不令人惊讶，因为相关结节病抗原(S)的入口很可能是通过呼吸道粘膜途径进入的。在结节病患者中，呼吸道粘膜受累的临床表现为呼吸道阻塞和鼻塞，并与顽固性和进展性疾病有关。结节病的上皮和呼吸道粘膜表现在非裔美国人中更为常见，这类患者的发病率和死亡率不成比例地高于非裔美国人。尽管有这些数据，但呼吸道上皮在调节结节样炎症和纤维化中的作用尚未被研究。我们推测，结节病的呼吸道上皮和粘膜反应可能通过释放调节粘膜炎症细胞的流入和成熟，最终导致组织纤维化的介质来影响疾病的发病机制。我们认为鼻黏膜上皮为研究这些假说提供了一个理想的方法，因为结节病的鼻部症状发生率很高，鼻黏膜反应为其他疾病提供了有趣的见解，但也代表了结节病的一种新方法，鼻部研究是安全和可行的，很可能进行纵向随访研究。我们建议通过从波士顿医学中心的结节病诊所招募一组结节病患者来描述该人群鼻部疾病的患病率、病因和免疫病理学。结果将与结节病的表型相关。我们相信，这些研究将挑战目前的假设，即结节病完全是Th1介导的疾病，并可能为根据鼻黏膜反应对结节病进行分类提供新的途径。此外，这项工作应为有关结节病的进一步研究提供基础。(摘要结束)

DESCRIPTION (provided by applicant): The respiratory epithelium plays a pathogenic role in airway and lung disease by regulating mucosal inflammation and tissue fibrosis. Sarcoidosis is associated with epithelial activation and mucosal inflammation. Granuloma formation is typically bronchocentric and certain cytokines such as osteopontin, interferon gamma and interleukin-4 are up-regulated in sarcoid epithelial cells. This is perhaps not surprising as the portal of entry of relevant sarcoidosis antigen(s) is likely to be via the respiratory mucosal route. In sarcoid patients respiratory mucosal involvement manifests clinically as airway obstruction and nasal congestion and has been associated with recalcitrant and progressive disease. Epithelial and respiratory mucosal manifestations of sarcoidosis are more common in African Americans, a group of patients that have disproportionately more morbidity and mortality from sarcoidosis. Despite these data the role of the respiratory epithelium in regulating sarcoidal inflammation and fibrosis has not been studied. We hypothesize that respiratory epithelial and mucosal responses in sarcoidosis may influence disease pathogenesis by releasing mediators which regulate the influx and maturation of mucosal inflammatory cells and ultimately tissue fibrosis. We believe that the nasal epithelium provides an ideal approach to study these hypotheses because there is a high prevalence of nasal symptoms in sarcoidosis, the fact that nasal mucosal responses have provided interesting insights into other diseases yet represent a novel approach to sarcoidosis, and nasal studies are safe and feasible with a high likelihood for longitudinal follow up studies. We propose to characterize the prevalence, etiology and immuno-pathology of nasal disease in this population by recruiting a cohort of sarcoid patients from the Sarcoidosis Clinic at Boston Medical Center. Results will be correlated with sarcoid disease phenotype. We believe that these studies will challenge the current hypothesis that sarcoidosis is exclusively a Th1 mediated disease and may provide novel avenues to classify sarcoidosis based on nasal mucosal responses. Furthermore this work should provide the basis for additional studies pertaining to sarcoidosis. (End of Abstract)