Ontogeny and Function of Early-Life Pulmonary Dendritic Cells

项目摘要/摘要 早产是美国婴儿死亡的主要原因，这些婴儿的肺不成熟 是一个主要原因。作为气体交换的器官，有效的肺功能对患者的生存至关重要。 刚出生的。出生时，早产儿的肺处于囊状发育阶段，与 成熟的成人肺。这些未成熟的肺在出生时首先接触到空气中的物质和微生物，并且 因此需要做好防御的准备。树突状细胞(DC)在这种屏障的防御和启动中起着关键作用。 免疫，然而，我们对这些未成熟肺中的DC的了解是有限的。我对我的调查 新生儿肺在早期DC中表现出以前未知的表型异质性。 车厢。此外，这些新生的肺DC亚群在转录上与它们的 在新生儿后期阶段的对应者。总而言之，我们的数据支持这样一种观点，即球状的DC间隔 分期肺在表型和功能上与成人不同。这些观察结果导致了我们 假设新生儿肺具有表型和功能不同的阶段特异性 肺部疾病控制中心。这一假设将通过以下具体目标来解决：目标1：审问 囊状期肺树突状细胞的个体发育和目的2：确定囊状期DC的功能。这两个都是 AIMS将与包括成熟肺在内的其他肺发育阶段进行比较。这些目标 将从个体发育和功能的角度阐明球囊期DC室，并将揭示其 新生儿肺部炎症的临床意义。这项拟议的研究将是第一次对 出生时肺树突状细胞及其在炎症中的作用。

PROJECT SUMMARY/ABSTRACT Premature birth is a leading cause of infant mortality in the United States, and lung immaturity in these babies is a major cause. As the organ of gas exchange, efficient lung function is critical for the survival of the newborn. At birth, premature lungs are in the saccular developmental stage, an immature state compared to the mature adult lungs. These immature lungs are first exposed to airborne material and microbes at birth, and thus need to be poised for defense. Dendritic cells (DC) play a key role in this barrier defense and initiating immunity, however, our understanding of DCs in these immature lungs is limited. My investigations into newborn lungs have revealed previously unknown phenotypic heterogeneity within the early-life DC compartment. Furthermore, these newborn lung DC subsets are transcriptionally distinct from their counterparts in later neonatal stages. Together our data support the idea that the DC compartment in saccular stage lungs is phenotypically and functionally distinct from the adult. These observations lead to our hypothesize that newborn lungs contain phenotypically and functionally heterogeneous stage-specific lung DCs. This hypothesis will be addressed through the following specific aims: Aim1: interrogate the ontogeny of saccular stage lung DCs, and Aim 2: Determine the functions of saccular stage DCs. Both of these aims will be performed in comparison to other lung development stages, including mature lungs. These aims will elucidate the saccular stage DC compartment in terms of ontogeny and function, and will reveal its significance in neonatal lung inflammation. The proposed research will be the first comprehensive analysis of the lung DC compartment at birth and its role in inflammation.