Oncostatin M as a mediator of adipose tissue immune balance

项目摘要/摘要 脂肪组织炎症直接导致肥胖患者的整体炎症状态，包括白细胞。 是脂肪细胞功能调节(或失调)的主要参与者。促炎细胞因子， OSM是由脂肪组织的肥大细胞、巨噬细胞和T细胞产生的。我们最近 已发表的数据表明，脂肪细胞通过其受体(OSMR)缺乏OSM信号导致脂肪组织 炎症和肥大细胞数量增加。与肥大细胞聚集有关的确切信号仍然存在 未知。我们将在这项提案中尝试解决这些问题。具体地说，我们将测试 假设脂肪细胞OSM信号是脂肪细胞-白细胞串扰的中介。我们最新的发现 是本提案具体目标的基础：(1)研究脂肪细胞OSM-OSMR信号转导的作用 作为肥大细胞增殖和成熟的调节者；以及(2)阐明肥大细胞对 WAT OSM表达与T细胞活化完成这些目标将有助于通过以下方式确定这些机制 在脂肪细胞和白细胞水平上，哪个OSM-OSMR信号与脂肪有关 免疫平衡。最重要的是，建议的研究是建立在从我的 K01奖，同时代表着K01项目的新的和合乎逻辑的延伸。从这些数据中生成的数据 研究将成为未来R01提案的基础，旨在研究脂肪之间的相互作用 组织细胞外基质和免疫细胞，这与我长期的研究目标是一致的。

PROJECT SUMMARY/ABSTRACT Adipose tissue inflammation directly contributes to the overall inflammatory state in obesity, with leukocytes being major players in the regulation (or dysregulation) of adipocyte function. The pro-inflammatory cytokine, oncostatin M (OSM), is produced by adipose tissue mast cells, macrophages, and T cells. Our recently published data suggest that lack of adipocyte OSM signaling via its receptor (OSMR) leads to adipose tissue inflammation and increased mast cell number. The exact signals involved in this mast cell accumulation remain unknown. We will attempt to address these questions in this proposal. Specifically, we will test the overarching hypothesis that adipocyte OSM signaling is a mediator of adipocyte-leukocyte crosstalk. Our recent findings are the basis for the specific aims of this proposal: (1) Investigate the role of adipocyte OSM-OSMR signaling as a regulator of WAT mast cell proliferation and maturation; and (2) Elucidate the contribution of mast cells to WAT OSM expression and T cell activation. The completion of these aims will help identify the mechanisms by which OSM-OSMR signaling, at the levels of both the adipocyte and the leukocyte, contributes to adipose immune balance. Most importantly, the proposed studies build upon data and experience obtained from my K01 award while representing a new and logical extension of the K01 project. Data generated from these studies will form the basis for future R01 proposals designed to investigate the interactions of the adipose tissue extracellular matrix and immune cells, which is consistent with my long-term research goal.