Results and Problems in Cell Differentiation最新文献

Tumor associated macrophages (TAMs) are one of the most prominent immune cells in the breast tumor microenvironment (TME). TAMs are categorised into classically activated anti-tumorigenic M1 and alternatively activated pro-tumorigenic M2 macrophages. TAMs are known to promote cancer pathogenesis by facilitating cancer cell and cancer stem cell growth, angiogenesis, immune evasion, invasion, and migration. Consequently, TAMs drive cancer progression towards metastasis. This chapter describes the role of TME in driving monocyte recruitment and polarization toward the M2 phenotype. We also illustrate the modalities of intercellular networking such as paracrine signaling, exosomes, and tunneling nanotubes (TNTs) that TAMs and cancer cells employ within TME to communicate with each other and with other cells of TME to facilitate the dynamic process of cancer progression. Finally, we discuss the clinical implications of TAMs in breast cancer and potential therapeutic strategies targeting TAM recruitment, polarization, and TAM-mediated immune evasion for effective cancer therapy.

Plasmodesmata are conduits in plant cell walls that allow neighboring cells to communicate and exchange resources. Despite their central importance to plant development and physiology, our understanding of plasmodesmata is relatively limited compared to other subcellular structures. In recent years, technical advances in electron microscopy, mass spectrometry, and phylogenomics have illuminated the structure, composition, and evolution of plasmodesmata in diverse plant lineages. In parallel, forward genetic screens have revealed key signaling pathways that converge to regulate plasmodesmatal transport, including chloroplast-derived retrograde signaling, phytohormone signaling, and metabolic regulation by the conserved eukaryotic Target of Rapamycin kinase. This review summarizes our current knowledge of the structure, evolution, and regulation of plasmodesmatal transport in plants.

Among factors like hormonal imbalance and uterine condition, oocyte quality is regarded as one of the key factors involved in age-related decline in the reproductive capacity. Here, are discussions about the functions played by organelles within the oocyte in forming the next generation that is more suitable for survival. Many insights on the adaptation to aging and maintenance of quality can be obtained from: interactions between mitochondria and other organelles that enable the long life of primordial oocytes; characteristics of organelle interactions after breaking dormancy from primary oocytes to mature oocytes; and characteristics of interactions between mitochondria and other organelles of aged oocytes collected during the ovulatory cycle from elderly individuals and animals. This information would potentially be beneficial to the development of future therapeutic methods or agents.

Multicellular organisms require cell-to-cell communication to maintain homeostasis and thrive. For cells to communicate, a network of filamentous, actin-rich tunneling nanotubes (TNTs) plays a pivotal role in facilitating efficient cell-to-cell communication by connecting the cytoplasm of adjacent or distant cells. Substantial documentation indicates that diverse cell types employ TNTs in a sophisticated and intricately organized fashion for both long and short-distance communication. Paradoxically, several pathogens, including viruses, exploit the structural integrity of TNTs to facilitate viral entry and rapid cell-to-cell spread. These pathogens utilize a "surfing" mechanism or intracellular transport along TNTs to bypass high-traffic cellular regions and evade immune surveillance and neutralization. Although TNTs are present across various cell types in healthy tissue, their magnitude is increased in the presence of viruses. This heightened induction significantly amplifies the role of TNTs in exacerbating disease manifestations, severity, and subsequent complications. Despite significant advancements in TNT research within the realm of infectious diseases, further studies are imperative to gain a precise understanding of TNTs' roles in diverse pathological conditions. Such investigations are essential for the development of novel therapeutic strategies aimed at leveraging TNT-associated mechanisms for clinical applications. In this chapter, we emphasize the significance of TNTs in the life cycle of viruses, showcasing the potential for a targeted approach to impede virus-host cell interactions during the initial stages of viral infections. This approach holds promise for intervention and prevention strategies.

Monocyte/macrophages are cells of myeloid origin which play critical roles in innate and adaptive immune responses as well as surveillance and tissue repair. Only recently, the role of monocytes/macrophages in acute and chronic HIV Infection has become accepted. Here, we will focus on monocyte/macrophages on transmigration events and their role as viral reservoirs.

Myeloid cells, including monocytes, macrophages, dendritic cells, and polymorphonuclear cells are key components of homeostasis maintenance and immune response. Among the myeloid lineage, macrophages stand out as highly versatile cells that safeguard tissue functions but also sense and respond to potentially harmful microenvironmental cues. Numerous studies have demonstrated that the nutritional status and macronutrient availability affect macrophage identity and function. However, the exact mechanistic links between macronutrient intake and cellular metabolic shifts are only beginning to be understood. In this chapter, we explore how dietary "macros"-carbohydrates, fats, and amino acids-impact the immunomodulatory activity of macrophages in healthy and inflamed tissues.

Viruses are vehicles to exchange genetic information and proteins between cells and organisms by infecting their target cells either cell-free, or depending on cell-cell contacts. Several viruses like certain retroviruses or herpesviruses transmit by both mechanisms. However, viruses have also evolved the properties to exchange proteins between cells independent of viral particle formation. This exchange of viral proteins can be directed to target cells prior to infection to interfere with restriction factors and intrinsic immunity, thus, making the target cell prone to infection. However, also bystander cells, e.g. immune cell populations, can be targeted by viral proteins to dampen antiviral responses. Mechanistically, viruses exploit several routes of cell-cell communication to exchange viral proteins like the formation of extracellular vesicles or the formation of long-distance connections like tunneling nanotubes. Although it is known that viral nucleic acids can be transferred between cells as well, this chapter concentrates on viral proteins of human pathogenic viruses covering all Baltimore classes and summarizes our current knowledge on intercellular transport of viral proteins between cells.

Intracellular protozoan pathogens have to negotiate the internal environment of the host cell they find themselves in, as well as manipulate the host cell to ensure their own survival, replication, and dissemination. The transfer of key effector molecules from the pathogen to the host cell is crucial to this interaction and is technically more demanding to study as compared to an extracellular pathogen. While several effector molecules have been identified, the mechanisms and conditions underlying their transfer to the host cell remain partly or entirely unknown. Improvements in experimental systems have revealed tantalizing details of such intercellular transfer, which form the subject of this chapter.

Tissue-resident macrophages are best known for their indispensable role in immunological reactions, where they contribute to immune defense and resolution of inflammation. However, recent studies have also uncovered that they provide crucial tissue-specific functions that support organ homeostasis and maintenance. Accordingly, defects in macrophage function or development can disrupt the delicate balance of organ homeostasis, leading to pathological conditions. Therefore, understanding the functions and development of macrophages within a tissue is critical for comprehending the interplay between immune and stromal cells, which together maintain organ physiology. This knowledge has clinical implications, such as in organ transplantation or irradiation, where monocyte-derived cells with different functions may replace the original macrophage population. In this chapter, we aim to provide an overview of the tissue-specific homeostatic functions of various macrophage populations, emphasizing that macrophages are essential components of each organ and play a vital role in ensuring the organism's survival, beyond their role in immunity.

Solid organ transplantation (SOT) offers life-saving therapy for patients with organ failure, yet chronic rejection remains a significant challenge despite advances in immunosuppression. Macrophages are central to chronic rejection, orchestrating fibrosis, and tissue damage. Since it became clear that histone deacetylases (HDACs), a family of epigenetic regulators, modulate macrophage function and polarization and eventually affect fibrosis progression, the HDACs modulation has gained great importance. This review explores the role of HDACs in chronic rejection, focusing on their impact on macrophage polarization and fibrosis. While some HDACs promote M2 polarization and fibrosis, others inhibit these processes, highlighting the complexity of HDAC function. Targeting HDACs holds promise as a therapeutic strategy for chronic rejection, offering a potential approach for intervention in transplant recipients. However, further research is needed to elucidate the specific roles of individual HDAC isoforms and their inhibition in chronic rejection.