Immune regulation of tissue iron in health and disease

健康和疾病中组织铁的免疫调节

基本信息

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
项目类别：
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&apos 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

项目摘要

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慢性疾病中同时发生，包括炎症性肠病（IBD）、感染、癌症。贫血通常难以治疗这些疾病，并且贫血和贫血的影响贫血疗法对疾病结果的影响尚不明确。因此，存在重大的医疗需求更好地了解贫血和炎症性疾病之间的因果关系。最好定义的链接之一介于贫血和炎症之间的是一种称为铁调素的肽激素，它能严重抑制铁的释放来自细胞内储存。铁调素水平通常在炎症期间急剧增加，并可能导致贫血的一种形式称为炎症性贫血 (AI)。相反，与炎症相关的疾病大量出血会导致一种独特形式的贫血，称为缺铁性贫血 (IDA)，其中铁调素水平被抑制。本研究提案的基本重点是：i.) 调查影响铁调素对炎症性疾病的影响，ii.) 鉴定表达铁调素的细胞群及其炎症期间的伴侣铁转运蛋白，以及 iii.) 通过不同的方法确定铁调节的影响细胞群对炎症性疾病解决的影响。我将采用创新技术方法并开发新工具来定义铁调素和铁转运蛋白在化学诱导过程中的作用肠道损伤、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体内铁的新型细胞介质的调节和功能意义肠道。这些发现将为正在进行的针对组织的疗法的开发工作提供重要信息炎症性疾病背景下的修复和贫血。