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Nature Communications Jul 2023Endo-lysosomes transport along microtubules and clustering in the perinuclear area are two necessary steps for microbes to activate specialized phagocyte functions. We...
Endo-lysosomes transport along microtubules and clustering in the perinuclear area are two necessary steps for microbes to activate specialized phagocyte functions. We report that RUN and FYVE domain-containing protein 3 (RUFY3) exists as two alternative isoforms distinguishable by the presence of a C-terminal FYVE domain and by their affinity for phosphatidylinositol 3-phosphate on endosomal membranes. The FYVE domain-bearing isoform (iRUFY3) is preferentially expressed in primary immune cells and up-regulated upon activation by microbes and Interferons. iRUFY3 is necessary for ARL8b + /LAMP1+ endo-lysosomes positioning in the pericentriolar organelles cloud of LPS-activated macrophages. We show that iRUFY3 controls macrophages migration, MHC II presentation and responses to Interferon-γ, while being important for intracellular Salmonella replication. Specific inactivation of rufy3 in phagocytes leads to aggravated pathologies in mouse upon LPS injection or bacterial pneumonia. This study highlights the role of iRUFY3 in controlling endo-lysosomal dynamics, which contributes to phagocyte activation and immune response regulation.
Topics: Animals; Mice; Antigen Presentation; Endosomes; Lipopolysaccharides; Lysosomes; Phagocytes
PubMed: 37463962
DOI: 10.1038/s41467-023-40062-x -
Frontiers in Immunology 2023
Topics: Gene Expression Regulation; Macrophages
PubMed: 38022640
DOI: 10.3389/fimmu.2023.1321064 -
Blood Aug 2023
Topics: Monocytes; Epigenesis, Genetic
PubMed: 37590027
DOI: 10.1182/blood.2023021298 -
Immunological Reviews Oct 2023Rheumatoid arthritis (RA) is a chronic inflammatory disease of the synovial joints that affects ~1% of the human population. Joint swelling and bone erosion, hallmarks... (Review)
Review
Rheumatoid arthritis (RA) is a chronic inflammatory disease of the synovial joints that affects ~1% of the human population. Joint swelling and bone erosion, hallmarks of RA, contribute to disability and, sometimes, loss of life. Mechanistically, disease is driven by immune dysregulation characterized by circulating autoantibodies, inflammatory mediators, tissue degradative enzymes, and metabolic dysfunction of resident stromal and recruited immune cells. Cell death by apoptosis has been therapeutically explored in animal models of RA due to the comparisons drawn between synovial hyperplasia and paucity of apoptosis in RA with the malignant transformation of cancer cells. Several efforts to induce cell death have shown benefits in reducing the development and/or severity of the disease. Apoptotic cells are cleared by phagocytes in a process known as efferocytosis, which differs from microbial phagocytosis in its "immuno-silent," or anti-inflammatory, nature. Failures in efferocytosis have been linked to autoimmune disease, whereas administration of apoptotic cells in RA models effectively inhibits inflammatory indices, likely though efferocytosis-mediated resolution-promoting mechanisms. However, the nature of signaling pathways elicited and the molecular identity of clearance mediators in RA are understudied. Furthermore, canonical efferocytosis machinery elements also play important non-canonical functions in homeostasis and pathology. Here, we discuss the roles of efferocytosis machinery components in models of RA and discuss their potential involvement in disease pathophysiology.
Topics: Animals; Humans; Phagocytosis; Arthritis, Rheumatoid; Phagocytes; Autoimmune Diseases; Apoptosis
PubMed: 37507355
DOI: 10.1111/imr.13256 -
Pathology, Research and Practice Sep 2023Macrophages are plastic and functionally diverse, present in all tissues, and play a key role in organisms from development, homeostasis and repair, to immune responses... (Review)
Review
Macrophages are plastic and functionally diverse, present in all tissues, and play a key role in organisms from development, homeostasis and repair, to immune responses to pathogens. They are central to many disease states and have emerged as important therapeutic targets for many diseases. Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment (TME) and are key factors influencing cancer progression, metastasis and tumor recurrence. TAMs can be derived from different sources and exert different pro- or anti-tumor effects based on the type, stage and immune composition of the tumor. TAMs are highly heterogeneous and diverse, and have multiple functional phenotypes. There is still a great deal of controversy regarding the relationship between TAMs and prognosis of cancer patients. In this review, we summarize the characteristics of common markers of TAMs as well as explore the prognostic role of TAMs in different cancers including lung, breast, gastric, colorectal, esophageal and ovarian cancers.
Topics: Tumor-Associated Macrophages; Neoplasms; Humans; Biomarkers, Tumor; Prognosis; Immunosuppression Therapy
PubMed: 37544129
DOI: 10.1016/j.prp.2023.154739 -
Medicina (Kaunas, Lithuania) Nov 2023Idiopathic pulmonary fibrosis (IPF) is a devastating disease of unknown etiology with limited treatment options. The role of the immune system in IPF has received... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is a devastating disease of unknown etiology with limited treatment options. The role of the immune system in IPF has received increasing attention. Uncontrolled immune responses drive the onset and progression of IPF. This article provides an overview of the role of innate immune cells (including macrophages, neutrophils, mast cells, eosinophils, dendritic cells, nature killer cells, nature kill cells and γδ T cells) and adaptive immune cells (including Th1 cells, Th2 cells, Th9 cells, Th17 cells, Th22 cells, cytotoxic T cells, B lymphocytes and Treg cells) in IPF. In addition, we review the current status of pharmacological treatments for IPF and new developments in immunotherapy. A deeper comprehension of the immune system's function in IPF may contribute to the development of targeted immunomodulatory therapies that can alter the course of the disease.
Topics: Humans; Idiopathic Pulmonary Fibrosis; T-Lymphocytes, Regulatory; Macrophages; Neutrophils; Mast Cells
PubMed: 38004032
DOI: 10.3390/medicina59111984 -
Methods in Molecular Biology (Clifton,... 2024Macrophages are cells of the innate immune system, which contribute to the maintenance of tissue homeostasis and form the first line of defense against pathogens....
Macrophages are cells of the innate immune system, which contribute to the maintenance of tissue homeostasis and form the first line of defense against pathogens. Tissue-resident macrophages that originate from erythro-myeloid-progenitors in the yolk sac colonize the organs early during development and self-maintain in most organs throughout adulthood. Under homeostatic and pathological conditions, circulating monocytes infiltrate the tissue, where they differentiate into macrophages. However, particularly upon inflammation, phenotyping of these distinct macrophage populations using surface markers or antibody stainings is insufficient as their phenotypes converge, at least transiently. A well-established method for the developmental origin of different cell types is the use of in vivo fate-mapping models, where a fluorescent reporter will be expressed under the control of a cell type-specific promoter. Here, we describe the Cxcr4; Rosa26 mouse fate-mapping model, which labels hematopoietic stem cells and, thus, also monocytes and monocyte-derived macrophages while most tissue-resident macrophages are not targeted.
Topics: Animals; Mice; Macrophages; Monocytes; Antibodies; Coloring Agents; Disease Models, Animal; Hematopoietic Stem Cells
PubMed: 37639120
DOI: 10.1007/978-1-0716-3437-0_9 -
Frontiers in Immunology 2023Despite tremendous efforts to exploit effective therapeutic strategies, most glioblastoma (GBM) inevitably relapse and become resistant to therapies, including... (Review)
Review
Despite tremendous efforts to exploit effective therapeutic strategies, most glioblastoma (GBM) inevitably relapse and become resistant to therapies, including radiotherapy and immunotherapy. The tumor microenvironment (TME) of recurrent GBM (rGBM) is highly immunosuppressive, dominated by tumor-associated macrophages (TAMs). TAMs consist of tissue-resident microglia and monocyte-derived macrophages (MDMs), which are essential for favoring tumor growth, invasion, angiogenesis, immune suppression, and therapeutic resistance; however, restricted by the absence of potent methods, the heterogeneity and plasticity of TAMs in rGBM remain incompletely investigated. Recent application of single-cell technologies, such as single-cell RNA-sequencing has enabled us to decipher the unforeseen diversity and dynamics of TAMs and to identify new subsets of TAMs which regulate anti-tumor immunity. Here, we first review hallmarks of the TME, progress and challenges of immunotherapy, and the biology of TAMs in the context of rGBM, including their origins, categories, and functions. Next, from a single-cell perspective, we highlight recent findings regarding the distinctions between tissue-resident microglia and MDMs, the identification and characterization of specific TAM subsets, and the dynamic alterations of TAMs during tumor progression and treatment. Last, we briefly discuss the potential of TAM-targeted strategies for combination immunotherapy in rGBM. We anticipate the comprehensive understanding of the diversity and dynamics of TAMs in rGBM will shed light on further improvement of immunotherapeutic efficacy in rGBM.
Topics: Humans; Tumor-Associated Macrophages; Glioblastoma; Macrophages; Chronic Disease; Recurrence; Tumor Microenvironment
PubMed: 37731483
DOI: 10.3389/fimmu.2023.1238233 -
Aging Cell Dec 2023Advancements in longevity research have provided insights into the impact of cardiac aging on the structural and functional aspects of the heart. Notable changes include... (Review)
Review
Advancements in longevity research have provided insights into the impact of cardiac aging on the structural and functional aspects of the heart. Notable changes include the gradual remodeling of the myocardium, the occurrence of left ventricular hypertrophy, and the decline in both systolic and diastolic functions. Macrophages, a type of immune cell, play a pivotal role in innate immunity by serving as vigilant agents against pathogens, facilitating wound healing, and orchestrating the development of targeted acquired immune responses. Distinct subsets of macrophages are present within the cardiac tissue and demonstrate varied functions in response to myocardial injury. The differentiation of cardiac macrophages according to their developmental origin has proven to be a valuable strategy in identifying reparative macrophage populations, which originate from embryonic cells and reside within the tissue, as well as inflammatory macrophages, which are derived from monocytes and recruited to the heart. These subsets of macrophages possess unique characteristics and perform distinct functions. This review aims to summarize the current understanding of the roles and phenotypes of cardiac macrophages in various conditions, including the steady state, aging, and other pathological conditions. Additionally, it will highlight areas that require further investigation to expand our knowledge in this field.
Topics: Heart; Macrophages; Myocardium; Monocytes
PubMed: 37817547
DOI: 10.1111/acel.14008 -
Drug Resistance Updates : Reviews and... Mar 2024Macrophages are important components of the immune system. Mature macrophages can be recruited to tumor microenvironment that affect tumor cell proliferation, invasion... (Review)
Review
Macrophages are important components of the immune system. Mature macrophages can be recruited to tumor microenvironment that affect tumor cell proliferation, invasion and metastasis, extracellular matrix remodeling, immune suppression, as well as chemotherapy resistance. Classically activated type I macrophages (M1) exhibited marked tumor killing and phagocytosis. Therefore, using macrophages for adoptive cell therapy has attracted attention and become one of the most effective strategies for cancer treatment. Through cytokines and/or chemokines, macrophage can inhibit myeloid cells recruitment, and activate anti-tumor and immune killing functions. Applying macrophages for anti-tumor delivery is one of the most promising approaches for cancer therapy. This review article introduces the role of macrophages in tumor development and drug resistance, and the possible clinical application of targeting macrophages for overcoming drug resistance and enhancing cancer therapeutics, as well as its challenges.
Topics: Humans; Tumor-Associated Macrophages; Macrophages; Neoplasms; Cytokines; Tumor Microenvironment
PubMed: 38198845
DOI: 10.1016/j.drup.2023.101041