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: 10050481
• 负责人: Nicholas J. Bessman
• 金额: $ 47.08万
• 依托单位: RBHS-NEW JERSEY MEDICAL SCHOOL
• 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/10050481
• 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; Epithelial; Erythrocytes; Flow Cytometry; Health; Heart; Hemorrhage; Homeostasis; Human; Imaging Techniques; Immune; Immune Targeting; Immune system; Immunotherapy; Infection; Infection Control; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Intestines; Iron; Iron deficiency anemia; Link; Liver; Liver Cirrhosis; Malignant Neoplasms; Malignant neoplasm of liver; Mammals; Mass Spectrum Analysis; Measures; Mediating; Mediator of activation protein; 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; base; enteric infection; healing; hepcidin; imaging approach; immunoregulation; in vivo; innovation; macrophage; 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 贫血和炎症通常共同发生在慢性疾病中，包括炎症性肠病（IBD）， 感染和癌症。在这些疾病中，贫血通常是难治性的，并且贫血的影响和 贫血治疗对疾病结局的影响尚不明确。因此，存在显著的医学需求， 更好地了解贫血和炎症性疾病之间的因果关系。最佳定义链接之一 在贫血和炎症之间是一种肽激素，称为铁调素，它严重抑制铁的释放 从细胞内储存。铁调素水平通常在炎症期间显著增加，并且可以引起 一种形式的贫血称为炎症性贫血（AI）。相反，与炎症相关的疾病 大量出血会引起一种称为缺铁性贫血（IDA）独特形式的贫血，其中铁调素 水平被压制。本研究建议的基本重点是：i.）调查的影响 铁调素对炎性疾病的作用，ii.）鉴定表达铁调素的细胞群体及其 炎症期间的伴侣膜铁转运蛋白，和iii.）确定铁调制的影响， 细胞群体对炎症性疾病的解决。我将采用创新的技术 方法和开发新的工具来定义铁调素和膜铁转运蛋白在化学诱导的 肠道损伤、肠道感染和炎症诱发的癌症。总的来说，这些结果 研究将确定新的铁细胞介质的调节和功能意义， 肠子这些发现将为正在进行的开发针对组织的疗法的努力提供重要信息 炎症性疾病背景下的修复和贫血。