Significance Circulating Semaphorin 7a+ve Cells in Pulmonary Sarcoidosis

描述（由申请人提供）： 结节病是一种慢性炎症性疾病，通常导致进行性，不可治疗的病理。它可能是由未识别的遗传、感染和/或环境因素之间的复杂相互作用引起的，这些因素结合联合收割机诱导受影响组织中持续的肉芽肿形成。这些肉芽肿含有数量增加的单核细胞和CD 4 + T细胞，并伴有促炎细胞因子和趋化因子增加，以及调节性T细胞（TCLs）异常，其通常用于控制炎症。关于这些因素如何导致疾病活动的表型差异知之甚少。因此，虽然许多结节病患者病情稳定，在某些情况下甚至缓解，但约20%的患者将发展为疾病进展，在某些情况下导致死亡。在我们更好地了解这种疾病之前，预测临床过程和发现 新疗法 我们最近发现结节病患者的血液中含有几种独特的细胞群，这些细胞群在疾病发病机制中具有潜在的重要性。我们发现结节病患者循环纤维细胞数量增加，并且（与正常对照不同）这些细胞分泌促炎细胞因子的数量增加。我们还发现，类肉瘤患者的血液中含有一个独特的Treg群体，表达Semaphorin 7a，这些细胞似乎刺激过度的纤维细胞生长和细胞因子分泌。奇怪的是，纤维细胞和Sema 7a+ T细胞在患有严重或进行性疾病的结节病患者中最高，因此可能与疾病表型相关。 该基金检验了纤维细胞和/或Sema 7a+ TcR作为新诊断的肺结节病患者疾病进展的生物标志物的假设。在目标1中，我们将招募和描述一组结节病患者（和对照组），为拟议的研究创建生物储存库。在目标2和目标3中，我们将量化循环纤维细胞和Sema 7a+ TcB，并评估其预测目标1中招募的受试者的疾病进展的能力。将进行机制研究以确定纤维细胞-Treg相互作用的性质。希望这些研究将加深我们对结节病患者疾病进展的理解，并产生新的见解，从而产生新的治疗选择。

DESCRIPTION (provided by applicant): Sarcoidosis is a chronic inflammatory disease that often results in progressive, untreatable pathology. It likely results from complex interactions between unidentified genetic, infectious, and/or environmental factors that combine to induce ongoing granuloma formation in affected tissues. These granulomas contain increased numbers of monocytes and CD4+ T cells and are accompanied by increased proinflammatory cytokines and chemokines, as well as by abnormalities in regulatory T cells (Tregs) which normally function to control inflammation. Little is known about how these factors lead to phenotypic differences in disease activity. Thus, while many patients with sarcoidosis will stabilize and in some cases even remit, approximately 20% of patients will develop progressive disease that in some cases results in death. Until we understand this disease better, there is little hope for predicting the clinical course and finding new therapies. We have recently found that the blood of patients with sarcoidosis contains several unique cell populations with potential import in disease pathogenesis. We have found that sarcoid patients show increased numbers of circulating fibrocytes, and that (unlike normal controls) these cells secrete increased quantities of proinflammatory cytokines. We have also found that the blood of sarcoid patients contains a unique Treg population that expresses Semaphorin 7a, and that these cells appear to stimulate exaggerated fibrocyte outgrowth and cytokine secretion. Curiously, both fibrocytes and Sema 7a+ Tregs are most elevated in those sarcoid patients with severe or progressive disease and as such may be related to disease phenotype. This grant tests the hypothesis that fibrocytes and/or Sema 7a+ Tregs function as biomarkers of disease progression in patients with newly diagnosed pulmonary sarcoidosis. In aim 1 we will recruit and characterize a cohort of sarcoid patients (and controls) to create a biorepository for the proposed studies. In aims 2 and 3 we will quantify circulating fibrocytes and Sema 7a+ Tregs and assess their ability to predict disease progression in the subjects recruited in aim 1. Mechanistic studies will be performed to determine the nature of the fibrocyte-Treg interactions. It is hoped that these studies will deepen our understanding of disease progression in patients with sarcoidosis and lead to new insight that could lead to novel therapeutic options.