Immune regulation of tissue iron in health and disease

健康和疾病中组织铁的免疫调节

• 批准号: 10624432
• 负责人: Nicholas J. Bessman
• 金额: $ 45.83万
• 依托单位: RUTGERS BIOMEDICAL AND HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-09 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10624432
• 关键词: Anemia; Anemia due to Chronic Disorder; Arthritis; Automobile Driving; Biological Markers; Biopsy; Cancer Model; Cell Separation; Cells; Chemicals; Chronic Disease; Complication; Crohn' s disease; Data; Dendritic Cells; Development; Diabetes Mellitus; Dietary Iron; Disease; Disease Outcome; Epithelium; Erythrocytes; Flow Cytometry; Health; Heart failure; Hemorrhage; Homeostasis; Human; Imaging Techniques; Immune; Immune Targeting; Immune system; Immunotherapy; Infection; Infection Control; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Intestines; Iron; Iron deficiency anemia; Life; Link; Liver; Liver Cirrhosis; Macrophage; Malignant Neoplasms; Malignant neoplasm of liver; Mammals; Mass Spectrum Analysis; Measures; Mediating; Mediator; Medical; Modeling; Mouse Strains; Mucous Membrane; Nutritional Immunity; Nutritional Support; Outcome; Pathway interactions; Patients; Phagocytes; Play; Population; Predisposition; Production; Proteins; Recording of previous events; Recycling; Refractory; Regulation; Research; Research Proposals; Resolution; Role; Serum; System; Testing; Tissues; Tumor-infiltrating immune cells; Work; carcinogenesis; enteric infection; gut inflammation; healing; health determinants; hepcidin; imaging approach; immunoregulation; in vivo; innovation; metal transporting protein 1; mouse model; neutrophil; novel; novel therapeutic intervention; novel therapeutics; peptide hormone; programs; senescence; targeted treatment; therapy development; tissue repair; tool; tumor; tumor growth; uptake

PROJECT ABSTRACT Anemia and inflammation often co-occur in chronic diseases including inflammatory bowel disease (IBD), infection, and cancer. Anemia is often refractory to treatment in these diseases, and the impact of anemia and anemia therapies on disease outcome is poorly defined. Accordingly, there is a significant medical need to better understand the causal links between anemia and inflammatory diseases. One of the best defined links between anemia and inflammation is a peptide hormone called hepcidin, which critically inhibits iron release from intracellular stores. Hepcidin levels typically increase dramatically during inflammation, and can cause one form of anemia termed anemia of inflammation (AI). Conversely, inflammatory diseases associated with heavy bleeding cause a distinct form of anemia known as iron deficiency anemia (IDA), in which hepcidin levels are suppressed. The fundamental focus of this research proposal is to: i.) investigate the impact of hepcidin on inflammatory disease, ii.) identify cellular populations expressing hepcidin and its partner ferroportin during inflammation, and iii.) determine the impact of iron modulation by distinct cellular population on the resolution of inflammatory diseases. I will employ innovative technical approaches and develop new tools to define the role of hepcidin and ferroportin during chemically-induced intestinal damage, intestinal infection, and in inflammation-induced cancer. Collectively, results from these studies will define the regulation and functional significance of novel cellular mediators of iron within the intestine. These findings will critically inform ongoing efforts to develop therapies targeting tissue repair and anemia in the context of inflammatory diseases.

项目摘要 贫血和炎症经常在包括炎症性肠病（IBD）的慢性疾病中共同发生， 感染和癌症。贫血通常是这些疾病中治疗的难治性，以及贫血和 疾病预后的贫血疗法的定义很差。因此，有很大的医疗需求 更好地了解贫血与炎症性疾病之间的因果关系。最佳定义链接之一 贫血和炎症之间是一种称为肝素的肽激素，严重抑制铁释放 来自细胞内存储。肝素水平通常在炎症期间急剧增加，并可能导致 一种贫血形式称为炎症贫血（AI）。相反，与 大量出血会导致一种独特的贫血形式，称为铁缺乏贫血（IDA），其中肝素蛋白 水平被抑制。该研究建议的基本重点是：i。）调查影响 肝素性疾病的肝素，ii。）确定表达肝素及其的细胞种群 炎症期间的伴侣铁托蛋白，iii。）确定铁调节的影响 细胞种群在炎症性疾病的分辨率上。我将采用创新技术 方法并开发了新工具来定义肝素和铁蛋白在化学诱导过程中的作用 肠道损伤，肠道感染以及炎症诱导的癌症。总体而言，这些结果 研究将定义新型铁中铁的调节和功能意义 肠。这些发现将严重告知开发针对组织的疗法的努力 在炎症性疾病的背景下修复和贫血。

项目成果

Gut-innervating nociceptors regulate the intestinal microbiota to promote tissue protection.

• DOI: 10.1016/j.cell.2022.09.008
• 发表时间: 2022-10-27
• 期刊: CELL
• 影响因子: 64.5
• 作者: Zhang, Wen;Lyu, Mengze;Bessman, Nicholas J.;Xie, Zili;Arifuzzaman, Mohammad;Yano, Hiroshi;Parkhurst, Christopher N.;Chu, Coco;Zhou, Lei;Putzel, Gregory G.;Li, Ting-Ting;Jin, Wen-Bing;Zhou, Jordan;Hu, Hongzhen;Tsou, Amy M.;Guo, Chun-Jun;Artis, David
• 通讯作者: Artis, David

Dysregulation of ILC3s unleashes progression and immunotherapy resistance in colon cancer.

• DOI: 10.1016/j.cell.2021.07.029
• 发表时间: 2021-09-16
• 期刊: Cell
• 影响因子: 64.5
• 作者: Goc J;Lv M;Bessman NJ;Flamar AL;Sahota S;Suzuki H;Teng F;Putzel GG;JRI Live Cell Bank;Eberl G;Withers DR;Arthur JC;Shah MA;Sonnenberg GF
• 通讯作者: Sonnenberg GF