Regulierung der Immunsuppression durch CD163 bei Pyelonephritis und chronischer lymphatischer Leukämie

CD163对肾盂肾炎和慢性淋巴细胞白血病免疫抑制的调节

• 批准号: 509468008
• 负责人: Professor Dr. Daniel Robert Engel
• 金额: --
• 依托单位: Institut für Experimentelle Immunologie und Bildgebung
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/509468008?language=en
• 关键词: Regulierung; der; Immunsuppression; durch; CD163

Pyelonephritis (PN) is a condition defined by bacterial invasion of the renal parenchyma. While most patients exhibit a mild course of the disease, a fraction of elderly, immunodeficient and cancer patients develops severe PN, requiring hospitalization. However, the mechanisms, which cause increased susceptibility to bacterial infections, leading to severe inflammation and impairment of kidney function are not understood. Innate immune cells, such as macrophages, employ a very broad phenotypical and functional repertoire and modulate critical anti-bacterial immune responses. The hemoglobin (Hb) scavenger receptor CD163 plays an essential role in macrophages polarization towards an anti-inflammatory state and has been implicated in different types of cancer and immunological disorders. Preliminary data revealed a highly significant upregulation of CD163 in the kidney of human patients suffering from severe PN. Through this proposal, we aim to study whether the expression of CD163 on macrophages predispose to severe PN through immunosuppression. We aim to (I) Deconvolute the spatial proteome to study macrophage polarization in human PN, (II) clarify the spatial mechanism for macrophage polarization in human PN, (III) evaluate the potential of soluble CD163 as a biomarker in blood and urine of PN patients, (IV) investigate the mechanism of immune suppression in CLL through CD163+ macrophages, and (V) clarify the role of CD163+ macrophages in PN.

肾盂肾炎（PN）是一种由细菌侵入肾实质定义的疾病。虽然大多数患者表现出轻度病程，但一部分老年、免疫缺陷和癌症患者发展为重度PN，需要住院治疗。然而，引起对细菌感染的易感性增加，导致严重炎症和肾功能损害的机制尚不清楚。先天免疫细胞，如巨噬细胞，采用非常广泛的表型和功能库，并调节关键的抗细菌免疫应答。血红蛋白（Hb）清道夫受体CD163在巨噬细胞向抗炎状态极化中起重要作用，并与不同类型的癌症和免疫性疾病有关。初步数据显示，在患有严重PN的人类患者的肾脏中，CD163高度显著上调。通过这个提议，我们的目的是研究巨噬细胞上CD163的表达是否通过免疫抑制而使严重PN易感。我们的目标是（I）解卷积空间蛋白质组以研究人PN中的巨噬细胞极化，（II）阐明人PN中巨噬细胞极化的空间机制，（III）评估可溶性CD 163作为PN患者血液和尿液中的生物标志物的潜力，（IV）研究CLL中通过CD 163+巨噬细胞的免疫抑制机制，阐明CD 163+巨噬细胞在PN中的作用。