Solute carrier proteins in efferocytosis and inflammation

胞吞作用和炎症中的溶质载体蛋白

• 批准号: 10199477
• 负责人: Kodi S Ravichandran
• 金额: $ 59.37万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-25 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10199477
• 关键词: Acute Renal Failure with Renal Papillary Necrosis; Address; Amino Acids; Anti-Inflammatory Agents; Apoptosis; Apoptotic; Atherosclerosis; Autoimmune Diseases; Binding; Biological Process; Biology; Carrier Proteins; Cell membrane; Cells; Cellular Membrane; Chronic; Communication; Defect; Dendritic Cells; Development; Digestion; Disease; Drug Targeting; Eating; Epithelial Cells; Evolution; Excision; Family; Family member; Fibroblasts; G-Protein-Coupled Receptors; Gene Family; Gene Proteins; Genes; Human; Human Genome; Immune system; Impairment; Infection; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Inflammatory Response; Insecta; Intestines; Ions; Knowledge; Life; Ligands; Link; Lung Inflammation; Mediating; Membrane Proteins; Modeling; Mus; Mutation; Nature; Nematoda; Organ; Organism; Pathologic; Phagocytes; Phagocytosis; Phase; Play; Process; Protein Family; Regulation; Role; Series; Signal Transduction; Testing; Therapeutic; Tissues; Work; aerobic glycolysis; base; cell age; cell injury; glucose uptake; human disease; insight; macrophage; member; prevent; public health relevance; receptor; solute; transcriptome sequencing; uptake; urea transporter

Abstract: SOLUTE CARRIER (SLC) PROTEINS IN EFFEROCYTOSIS AND INFLAMMATION: It is truly remarkable that our bodies turn over on average about one million cells every second of life. The cells that are turned over, predominantly by the process of apoptosis, include excess cells generated as part of normal development, used/aged cells, and damaged cells arising from disease or infections. The efficient removal of such apoptotic cells is important for ‘making space’ for replacement by living cells, preventing inflammation, maintaining the function of the tissue/organ, and in turn, a healthy organism. The efficient removal of the dying cells occurs via the process of ‘efferocytosis’, and is done by professional phagocytes (such as macrophages and immature dendritic cells) or neighboring cells (e.g. fibroblasts, epithelial cells) within a given tissue. Efferocytosis, which involves ligands on apoptotic cells and specific receptors on phagocytes, is very efficient, and actively anti-inflammatory. However, impaired clearance of apoptotic cells results in the accumulation of dead cells, and the resulting chronic inflammation linked to a number of pathological conditions such as atherosclerosis, lung inflammation, and inflammatory bowel diseases. While significant progress has been made in understanding apoptotic cell recognition and efferocytic uptake in recent years, significant gaps remain. Solute carrier (SLC) proteins are membrane proteins that selectively conduct ions, metabolites, and aminoacids across the plasma membrane, and specific internal cellular membranes. In the human genome, SLCs represent the second largest family (after the GPCRs), with ~400 SLC family members. Despite ~100 human diseases being linked to mutations in SLC genes, the SLC family is relatively understided, including in the immune system 7,8. This may in part be because the SLCs functionally characterized have often been in isolation, and not many SLCs are studied as part of a larger biological process. Recently, while studying phagocytes taking up apoptotic cells, we unexpectedly came across a coordinated regulation of >30 members of the Slc gene family (Morioka et al., Nature 2018; Perry et al, Nature Cell Biol., 2019). This proposal tests the hypothesis that SLC proteins can play key roles in different phases of efferocytosis, and that sequential use of specific SLCs during efferocytosis facilitates communication between phagocytes contributes to maintaining an anti-inflammatory state within tissues.

文摘：溶质载体（SLC）蛋白在红细胞增生和炎症中的作用：