Regulierung der Immunsuppression durch CD163 bei Pyelonephritis und chronischer lymphatischer Leukämie

肾盂肾炎（PN）是一种由细菌侵入肾实质所定义的疾病。虽然大多数患者表现出轻微的病程，但一小部分老年人、免疫缺陷和癌症患者会出现严重的PN，需要住院治疗。然而，导致对细菌感染易感性增加，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，具有非常广泛的表型和功能库，并调节关键的抗菌免疫反应。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疾病有关。初步数据显示，患有严重PN的人类患者肾脏中CD163的表达高度显著上调。通过本提案，我们旨在研究CD163在巨噬细胞上的表达是否会通过免疫抑制导致严重PN的发生。我们的目标是：(I)解解空间蛋白质组来研究人类PN中巨噬细胞极化，（II）阐明人类PN中巨噬细胞极化的空间机制，（III）评估可溶性CD163作为PN患者血液和尿液生物标志物的潜力，（IV）通过CD163+巨噬细胞研究CLL免疫抑制机制，(V)阐明CD163+巨噬细胞在PN中的作用。

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.