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Frontiers in Immunology 2021Periodontitis (PD) is a common chronic infectious disease. The local inflammatory response in the host may cause the destruction of supporting periodontal tissue.... (Review)
Review
Periodontitis (PD) is a common chronic infectious disease. The local inflammatory response in the host may cause the destruction of supporting periodontal tissue. Macrophages play a variety of roles in PD, including regulatory and phagocytosis. Moreover, under the induction of different factors, macrophages polarize and form different functional phenotypes. Among them, M1-type macrophages with proinflammatory functions and M2-type macrophages with anti-inflammatory functions are the most representative, and both of them can regulate the tendency of the immune system to exert proinflammatory or anti-inflammatory functions. M1 and M2 macrophages are involved in the destructive and reparative stages of PD. Due to the complex microenvironment of PD, the dynamic development of PD, and various local mediators, increasing attention has been given to the study of macrophage polarization in PD. This review summarizes the role of macrophage polarization in the development of PD and its research progress.
Topics: Animals; Cell Polarity; Cytokines; Humans; Janus Kinases; Macrophages; NF-kappa B; Periodontitis; Periodontium; STAT Transcription Factors; Signal Transduction
PubMed: 34950140
DOI: 10.3389/fimmu.2021.763334 -
Frontiers in Immunology 2021Macrophages are dynamic cells that play critical roles in the induction and resolution of sterile inflammation. In this review, we will compile and interpret recent... (Review)
Review
Macrophages are dynamic cells that play critical roles in the induction and resolution of sterile inflammation. In this review, we will compile and interpret recent findings on the plasticity of macrophages and how these cells contribute to the development of non-infectious inflammatory diseases, with a particular focus on allergic and autoimmune disorders. The critical roles of macrophages in the resolution of inflammation will then be examined, emphasizing the ability of macrophages to clear apoptotic immune cells. Rheumatoid arthritis (RA) is a chronic autoimmune-driven spectrum of diseases where persistent inflammation results in synovial hyperplasia and excessive immune cell accumulation, leading to remodeling and reduced function in affected joints. Macrophages are central to the pathophysiology of RA, driving episodic cycles of chronic inflammation and tissue destruction. RA patients have increased numbers of active M1 polarized pro-inflammatory macrophages and few or inactive M2 type cells. This imbalance in macrophage homeostasis is a main contributor to pro-inflammatory mediators in RA, resulting in continual activation of immune and stromal populations and accelerated tissue remodeling. Modulation of macrophage phenotype and function remains a key therapeutic goal for the treatment of this disease. Intriguingly, therapeutic intervention with glucocorticoids or other DMARDs promotes the re-polarization of M1 macrophages to an anti-inflammatory M2 phenotype; this reprogramming is dependent on metabolic changes to promote phenotypic switching. Allergic asthma is associated with Th2-polarised airway inflammation, structural remodeling of the large airways, and airway hyperresponsiveness. Macrophage polarization has a profound impact on asthma pathogenesis, as the response to allergen exposure is regulated by an intricate interplay between local immune factors including cytokines, chemokines and danger signals from neighboring cells. In the Th2-polarized environment characteristic of allergic asthma, high levels of IL-4 produced by locally infiltrating innate lymphoid cells and helper T cells promote the acquisition of an alternatively activated M2a phenotype in macrophages, with myriad effects on the local immune response and airway structure. Targeting regulators of macrophage plasticity is currently being pursued in the treatment of allergic asthma and other allergic diseases. Macrophages promote the re-balancing of pro-inflammatory responses towards pro-resolution responses and are thus central to the success of an inflammatory response. It has long been established that apoptosis supports monocyte and macrophage recruitment to sites of inflammation, facilitating subsequent corpse clearance. This drives resolution responses and mediates a phenotypic switch in the polarity of macrophages. However, the role of apoptotic cell-derived extracellular vesicles (ACdEV) in the recruitment and control of macrophage phenotype has received remarkably little attention. ACdEV are powerful mediators of intercellular communication, carrying a wealth of lipid and protein mediators that may modulate macrophage phenotype, including a cargo of active immune-modulating enzymes. The impact of such interactions may result in repair or disease in different contexts. In this review, we will discuss the origin, characterization, and activity of macrophages in sterile inflammatory diseases and the underlying mechanisms of macrophage polarization ACdEV and apoptotic cell clearance, in order to provide new insights into therapeutic strategies that could exploit the capabilities of these agile and responsive cells.
Topics: Animals; Autoimmune Diseases; Humans; Inflammation; Macrophages
PubMed: 34456917
DOI: 10.3389/fimmu.2021.708186 -
Frontiers in Immunology 2020Cartilage lesions and osteoarthritis (OA) presents an ever-increasing clinical and socioeconomic burden. Synovial inflammation and articular inflammatory environment are... (Review)
Review
Cartilage lesions and osteoarthritis (OA) presents an ever-increasing clinical and socioeconomic burden. Synovial inflammation and articular inflammatory environment are the key factor for chondrocytes apoptosis and hypertrophy, ectopic bone formation and OA progression. To effectively treat OA, it is critical to develop a drug that skews inflammation toward a pro-chondrogenic microenvironment. In this narrative and critical review, we aim to see the potential use of immune cells modulation or cell therapy as therapeutic alternatives to OA patients. Macrophages are immune cells that are present in synovial lining, with different roles depending on their subtypes. These cells can polarize to pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes, being the latter associated with wound-healing by the production of ARG-1 and pro-chondrogenic cytokines, such as IL-10, IL-1RA, and TGF-b. Emerging evidence reveals that macrophage shift can be determined by several stimuli, apart from the conventional IL-4, IL-13, and IL-10. Evidences show the potential of physical exercise to induce type 2 response, favoring M2 polarization. Moreover, macrophages in contact with oxLDL have effect on the production of anabolic mediators as TGF-b. In the same direction, type II collagen, that plays a critical role in development and maturation process of chondrocytes, can also induce M2 macrophages, increasing TGF-b. The mTOR pathway activation in macrophages was shown to be able to polarize macrophages , though further studies are required. The possibility to use mesenchymal stem cells (MSCs) in cartilage restoration have a more concrete literature, besides, MSCs also have the capability to induce M2 macrophages. In the other direction, M1 polarized macrophages inhibit the proliferation and viability of MSCs and impair their ability to immunosuppress the environment, preventing cartilage repair. Therefore, even though MSCs therapeutic researches advances, other sources of M2 polarization are attractive issues, and further studies will contribute to the possibility to manipulate this polarization and to use it as a therapeutic approach in OA patients.
Topics: Animals; Cartilage, Articular; Cell Polarity; Cell- and Tissue-Based Therapy; Humans; Immunomodulation; Macrophage Activation; Macrophages; Mesenchymal Stem Cells; Osteoarthritis; Regeneration; Synovitis
PubMed: 32117263
DOI: 10.3389/fimmu.2020.00111 -
Frontiers in Cell and Developmental... 2020Cell and tissue polarity due to the extracellular signaling and intracellular gene cascades, in turn, signals the directed cell behaviors and asymmetric tissue... (Review)
Review
Cell and tissue polarity due to the extracellular signaling and intracellular gene cascades, in turn, signals the directed cell behaviors and asymmetric tissue architectures that play a crucial role in organogenesis and embryogenesis. The notochord is a characteristic midline organ in chordate embryos that supports the body structure and produces positioning signaling. This review summarizes cellular and tissue-level polarities during notochord development in ascidians. At the early stage, planar cell polarity (PCP) is initialized, which drives cell convergence extension and migration to form a rod-like structure. Subsequently, the notochord undergoes a mesenchymal-epithelial transition, becoming an unusual epithelium in which cells have two opposing apical domains facing the extracellular lumen deposited between adjacent notochord cells controlled by apical-basal (AB) polarity. Cytoskeleton distribution is one of the main downstream events of cell polarity. Some cytoskeleton polarity patterns are a consequence of PCP: however, an additional polarized cytoskeleton, together with Rho signaling, might serve as a guide for correct AB polarity initiation in the notochord. In addition, the notochord's mechanical properties are associated with polarity establishment and transformation, which bridge signaling regulation and tissue mechanical properties that enable the coordinated organogenesis during embryo development.
PubMed: 33195278
DOI: 10.3389/fcell.2020.597446 -
Developmental Biology Jul 2022Cell polarity is regulated by both intrinsic properties of the cell and extrinsic factors in the environment. Wnts are secreted glycoproteins in graded distribution, and... (Review)
Review
Cell polarity is regulated by both intrinsic properties of the cell and extrinsic factors in the environment. Wnts are secreted glycoproteins in graded distribution, and they function as morphogens to instruct cell fate and as guidance cues to steer axon growth cone, respectively. Recent studies suggest that Wnts also instruct cell polarization in diverse contexts, by engaging cytoskeletal machineries or transcriptional mechanisms. Here we review the literature of cell polarity control by Wnt glycoproteins, with an emphasis on the nematode Caenorhabditis elegans, a multi-cellular organism in which the importance of polarity-inducing factors can be verified in vivo. In both embryonic and postembryonic cell lineages that undergo asymmetric division, Wnts act as directional signals to instruct the asymmetry of mitosis. In C. elegans, Wnts polarize neuroblasts to control their directional migration, and they also specify axon-dendrite polarity by providing spatial instruction for postmitotic neurons. Together this review summarizes recent advances and unsolved issues in cell polarity control by Wnt glycoproteins.
Topics: Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Cell Polarity; Glycoproteins; Wnt Proteins
PubMed: 35461833
DOI: 10.1016/j.ydbio.2022.04.007 -
Frontiers in Immunology 2020Neutrophils act as the first line of defense against invading pathogens. Although traditionally considered in context of their antimicrobial effector functions, the...
Neutrophils act as the first line of defense against invading pathogens. Although traditionally considered in context of their antimicrobial effector functions, the importance of tumor-associated neutrophils (TANs) in the development of cancer has become increasingly clear during the last decade. With regard to their high plasticity, neutrophils were shown to acquire an anti-tumorigenic N1 or a pro-tumorigenic N2 phenotype. Despite the urgent need to get a comprehensive understanding of the interaction of TANs with their tumor microenvironment, most studies still rely on murine tumor models. Here we present for the first time a polarization attempt to generate N1 and N2 neutrophils from primary human neutrophils . Our results underscore that N1-polarized neutrophils have a pro-inflammatory phenotype characterized among others by a higher level of intercellular adhesion molecule (ICAM)-1 and high secretion of interferon (IFN)γ-induced protein 10 (IP-10)/C-X-C motif chemokine 10 (CXCL10) and tumor necrosis factor (TNF). Further, we demonstrate that neutrophils incubated under a tumor-mimicking environment show a high cell surface expression of C-X-C motif chemokine receptor 2 (CXCR2) and secrete high levels of interleukin (IL)-8. These findings suggest that it is feasible to polarize blood-derived primary human neutrophils toward N1- and N2-like phenotypes . Further, we hypothesized that the presence of anti-inflammatory neutrophil phenotype is not a phenomenon limited to cancer but also occurs when neutrophils are infected with intracellular pathogens. Indeed, our findings indicate that N2-polarized neutrophils exert a markedly decreased capacity to kill the protozoan parasite and therefore permit parasite persistence.
Topics: Cell Culture Techniques; Cell Differentiation; Humans; Leishmania donovani; Neutrophils; Phenotype
PubMed: 32411122
DOI: 10.3389/fimmu.2020.00532 -
The Journal of Histochemistry and... Oct 2021Collagen has a major role in the structural organization of tendons. Picrosirius red (PSR) staining viewed under polarized light microscopy is the standard method to...
Collagen has a major role in the structural organization of tendons. Picrosirius red (PSR) staining viewed under polarized light microscopy is the standard method to evaluate the organization of collagen fibers in tissues. It is also used to distinguish between type I and type III collagen in tissue sections. However, accurate analysis and interpretation of PSR images are challenging because of technical factors and historical misconceptions. The aim of this study was to clarify whether collagen types I and III can be distinguished by PSR staining in rat Achilles tendons, using double immunohistochemistry as the positive control. Our findings showed that PSR staining viewed with polarized light microscopy was suitable for qualitative and quantitative assessment of total collagen but was not able to distinguish collagen types. We found it critical to use a polarizing microscope equipped with a rotating stage; tendon section orientation at 45° with respect to crossed polarizers was optimal for the qualitative and quantitative assessment of collagen organization. Immunohistochemistry was superior to PSR staining for detection of collagen type III. We also compared formalin and Bouin solution as fixatives. Both produced similar birefringence, but formalin-fixed tendons provided higher quality histological detail with both hematoxylin-eosin and immunostaining.
Topics: Animals; Azo Compounds; Collagen Type I; Collagen Type III; Rats; Rats, Sprague-Dawley; Staining and Labeling; Tendons
PubMed: 34549650
DOI: 10.1369/00221554211046777 -
Journal of Cell Science Aug 2014Cell polarity is characterised by differences in structure, composition and function between at least two poles of a cell. In epithelial cells, these spatial differences... (Review)
Review
Cell polarity is characterised by differences in structure, composition and function between at least two poles of a cell. In epithelial cells, these spatial differences allow for the formation of defined apical and basal membranes. It has been increasingly recognised that cell-matrix interactions and integrins play an essential role in creating epithelial cell polarity, although key gaps in our knowledge remain. This Commentary will discuss the mounting evidence for the role of integrins in polarising epithelial cells. We build a model in which both inside-out signals to polarise basement membrane assembly at the basal surface, and outside-in signals to control microtubule apical-basal orientation and vesicular trafficking are required for establishing and maintaining the orientation of epithelial cell polarity. Finally, we discuss the relevance of the basal integrin polarity axis to cancer. This article is part of a Minifocus on Establishing polarity.
Topics: Animals; Basement Membrane; Cell Polarity; Epithelial Cells; Humans; Integrins; Microtubules; Neoplasms
PubMed: 24994933
DOI: 10.1242/jcs.146142 -
Journal of Cell Science Apr 2017Cells exhibit morphological and molecular asymmetries that are broadly categorized as cell polarity. The cell polarity established in early embryos prefigures the... (Review)
Review
Cells exhibit morphological and molecular asymmetries that are broadly categorized as cell polarity. The cell polarity established in early embryos prefigures the macroscopic anatomical asymmetries characteristic of adult animals. For example, eggs and early embryos have polarized distributions of RNAs and proteins that generate global anterior/posterior and dorsal/ventral axes. The molecular programs that polarize embryos are subsequently reused in multiple contexts. Epithelial cells require apical/basal polarity to establish their barrier function. Migrating cells polarize in the direction of movement, creating distinct leading and trailing structures. Asymmetrically dividing stem cells partition different molecules between themselves and their daughter cells. Cell polarity can develop , be maintained through rounds of cell division and be dynamically remodeled. In this Cell Science at a Glance review and poster, we describe molecular asymmetries that underlie cell polarity in several cellular contexts. We highlight multiple developmental systems that first establish cell/developmental polarity, and then maintain it. Our poster showcases repeated use of the Par, Scribble and Crumbs polarity complexes, which drive the development of cell polarity in many cell types and organisms. We then briefly discuss the diverse and dynamic changes in cell polarity that occur during cell migration, asymmetric cell division and in planar polarized tissues.
Topics: Animals; Asymmetric Cell Division; Caenorhabditis elegans; Cell Movement; Cell Polarity; Humans; Multiprotein Complexes; Signal Transduction
PubMed: 28365593
DOI: 10.1242/jcs.188599 -
Journal of Integrative Plant Biology Jan 2020Cell polarity plays an important role in a wide range of biological processes in plant growth and development. Cell polarity is manifested as the asymmetric distribution... (Review)
Review
Cell polarity plays an important role in a wide range of biological processes in plant growth and development. Cell polarity is manifested as the asymmetric distribution of molecules, for example, proteins and lipids, at the plasma membrane and/or inside of a cell. Here, we summarize a few polarized proteins that have been characterized in plants and we review recent advances towards understanding the molecular mechanism for them to polarize at the plasma membrane. Multiple mechanisms, including membrane trafficking, cytoskeletal activities, and protein phosphorylation, and so forth define the polarized plasma membrane domains. Recent discoveries suggest that the polar positioning of the proteo-lipid membrane domain may instruct the formation of polarity complexes in plants. In this review, we highlight the factors and regulators for their functions in establishing the membrane asymmetries in plant development. Furthermore, we discuss a few outstanding questions to be addressed to better understand the mechanisms by which cell polarity is regulated in plants.
Topics: Cell Membrane; Cell Polarity; Homeostasis; Plant Cells; Plant Proteins; Plants
PubMed: 31889400
DOI: 10.1111/jipb.12904