CD157 and CD200 at the crossroads of endothelial remodeling and immune regulation.
Ontology highlight
ABSTRACT:
SUBMITTER: Katoh M
PROVIDER: S-EPMC6509431 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
Publications
CD157 and CD200 at the crossroads of endothelial remodeling and immune regulation.
Stem cell investigation 20190419
Similar Datasets
Project description:CD200 is a cell membrane glycoprotein that interacts with its structurally related receptor (CD200R) expressed on immune cells. We characterized CD200-CD200R interactions in human adult/juvenile (j/a) and fetal (f) skin and in in vivo prevascularized skin substitutes (vascDESS) prepared by co-culturing human dermal microvascular endothelial cells (HDMEC), containing both blood (BEC) and lymphatic (LEC) EC. We detected the highest expression of CD200 on lymphatic capillaries in j/a and f skin as well as in vascDESS in vivo, whereas it was only weakly expressed on blood capillaries. Notably, the highest CD200 levels were detected on LEC with enhanced Podoplanin expression, while reduced expression was observed on Podoplanin-low LEC. Further, qRT-PCR analysis revealed upregulated expression of some chemokines, including CC-chemokine ligand 21 (CCL21) in j/aCD200+ LEC, as compared to j/aCD200- LEC. The expression of CD200R was mainly detected on myeloid cells such as granulocytes, monocytes/macrophages, T cells in human peripheral blood, and human and rat skin. Functional immunoassays demonstrated specific binding of skin-derived CD200+ HDMEC to myeloid CD200R+ cells in vitro. Importantly, we confirmed enhanced CD200-CD200R interaction in vascDESS in vivo. We concluded that the CD200-CD200R axis plays a crucial role in regulating tissue inflammation during skin wound healing.
| S-EPMC8947338 | biostudies-literature
Project description:The CD200:CD200R1 inhibitory signaling pathway has been implicated in playing a prominent role in limiting inflammation in a wide range of inflammatory diseases. CD200R1 signaling inhibits the expression of proinflammatory molecules including tumor necrosis factor, interferons, and inducible nitric oxide synthase in response to selected stimuli. Unsurprisingly, due to the regulatory role that CD200R1 plays in multiple inflammatory pathways, an increasing number of parasitic, bacterial, and viral pathogens exploit this pathway to suppress host defenses. A complete understanding of the pathways regulated by CD200R1 signaling and the diverse mechanisms that pathogens have evolved to manipulate the CD200:CD200R1 pathway can help identify clinical situations where targeting this interaction can be of therapeutic benefit. In this review, we compare CD200R1 to other pathogen-targeted inhibitory receptors and highlight how this signaling pathway is utilized by a diverse number of pathogens and, therefore, may represent a novel targeting strategy for the treatment of infectious diseases.
| S-EPMC4617684 | biostudies-literature
Project description:CD200 is a widely distributed membrane glycoprotein that regulates myeloid cell activity through its interaction with an inhibitory receptor (CD200R). The interaction is of interest as a target for treating excessive inflammation and for treating leukemia. There are closely related proteins to CD200R that give activating signals making this a "paired receptor." We report X-ray crystallography structures for the inhibitory CD200R, the activating receptor CD200RLa, and a complex between CD200R and CD200. Both CD200 and CD200R contain two Ig-like domains and interact through their NH₂ terminal domains compatible with immunological synapse-like interactions occurring between myeloid cells and other CD200-expressing cells. The failure of the activating receptor to bind CD200 resides in subtle changes around the interface. CD200 has been acquired by herpes viruses to mimic the host interaction. CD200R has evolved rapidly presumably driven by pathogen pressure but it may also be important in homeostasis through interactions with commensal bacteria.
| S-EPMC3664923 | biostudies-literature
Project description:The infiltration of immune cells into the central nervous system mediates the development of autoimmune neuroinflammatory diseases. We previously showed that the loss of either Fabp5 or calnexin causes resistance to the induction of experimental autoimmune encephalomyelitis (EAE) in mice, an animal model of multiple sclerosis (MS). Here we show that brain endothelial cells lacking either Fabp5 or calnexin have an increased abundance of cell surface CD200 and soluble CD200 (sCD200) as well as decreased T-cell adhesion. In a tissue culture model of the blood-brain barrier, antagonizing the interaction of CD200 and sCD200 with T-cell CD200 receptor (CD200R1) via anti-CD200 blocking antibodies or the RNAi-mediated inhibition of CD200 production by endothelial cells increased T-cell adhesion and transmigration across monolayers of endothelial cells. Our findings demonstrate that sCD200 produced by brain endothelial cells regulates immune cell trafficking through the blood-brain barrier and is primarily responsible for preventing activated T-cells from entering the brain.
| S-EPMC11395061 | biostudies-literature
Project description:Pulmonary hypertension (PH) is a debilitating and life-threatening disease characterized by increased blood pressure within the pulmonary arteries. Adenosine monophosphate-activated protein kinase (AMPK) is a heterotrimeric serine-threonine kinase that contributes to the regulation of metabolic and redox signaling pathways. It has key roles in the regulation of cell survival and proliferation. The role of AMPK in PH is controversial because both inhibition and activation of AMPK are preventive against PH development. Some clinical studies found that metformin, the first-line antidiabetic drug and the canonical AMPK activator, has therapeutic efficacy during treatment of early-stage PH. Other study findings suggest the use of metformin is preferentially beneficial for treatment of PH associated with heart failure with preserved ejection fraction (PH-HFpEF). In this review, we discuss the "AMPK paradox" and highlight the differential effects of AMPK on pulmonary vasoconstriction and pulmonary vascular remodeling. We also review the effects of AMPK activators and inhibitors on rescue of preexisting PH in animals and include a discussion of gender differences in the response to metformin in PH.
| S-EPMC8217619 | biostudies-literature
Project description:Ectoenzyme and receptor BST-1/CD157 has been considered as a key molecule involved in the regulation of functional activity of cells in various tissues and organs. It is commonly accepted that CD157 catalyzes NAD+ hydrolysis and acts as a component of integrin adhesion receptor complex. Such properties are important for the regulatory role of CD157 in neuronal and glial cells: in addition to recently discovered role in the regulation of emotions, motor functions, and social behavior, CD157 might serve as an important component of innate immune reactions in the central nervous system. Activation of innate immune system in the brain occurs in response to infectious agents as well as in brain injury and neurodegeneration. As an example, in microglial cells, association of CD157 with CD11b/CD18 complex drives reactive gliosis and neuroinflammation evident in brain ischemia, chronic neurodegeneration, and aging. There are various non-substrate ligands of CD157 belonging to the family of extracellular matrix proteins (fibronectin, collagen I, finbrinogen, and laminin) whose activity is required for controlling cell adhesion and migration. Therefore, CD157 could control structural and functional integrity of the blood-brain barrier and barriergenesis. On the other hand, contribution of CD157 to the regulation of brain development is rather possible since in the embryonic brain, CD157 expression is very high, whereas in the adult brain, CD157 is expressed on neural stem cells and, presumably, is involved in the neurogenesis. Besides, CD157 could mediate astrocytes' action on neural stem and progenitor cells within neurogenic niches. In this review we will summarize how CD157 may affect brain plasticity acting as a molecule at the crossroad of neurogenesis, cerebral angiogenesis, and immune regulation.
| S-EPMC7693531 | biostudies-literature
Project description:Over the past 2 decades, the adaptor protein transducin β-like 1 (TBL1X) and its homolog TBL1XR1 have been shown to be upregulated in solid tumors and hematologic malignancies, and their overexpression is associated with poor clinical outcomes. Moreover, dysregulation of the TBL1 family of proteins has been implicated as a key component of oncogenic prosurvival signaling, cancer progression, and metastasis. Herein, we discuss how TBL1X and TBL1XR1 are required for the regulation of major transcriptional programs through the silencing mediator for tetanoid and thyroid hormone receptor (SMRT)/nuclear receptor corepressor (NCOR)/ B cell lymphoma 6 (BCL6) complex, Wnt/β catenin, and NF-κB signaling. We outline the utilization of tegavivint (Iterion Therapeutics), a first-in-class small molecule targeting the N-terminus domain of TBL1, as a novel therapeutic strategy in preclinical models of cancer and clinically. Although most published work has focused on the transcriptional role of TBL1X, we recently showed that in diffuse large B-cell lymphoma (DLBCL), the most common lymphoma subtype, genetic knockdown of TBL1X and treatment with tegavivint resulted in decreased expression of critical (onco)-proteins in a posttranscriptional/β-catenin-independent manner by promoting their proteasomal degradation through a Skp1/Cul1/F-box (SCF)/TBL1X supercomplex and potentially through the regulation of protein synthesis. However, given that TBL1X controls multiple oncogenic signaling pathways in cancer, treatment with tegavivint may ultimately result in drug resistance, providing the rationale for combination strategies. Although many questions related to TBL1X function remain to be answered in lymphoma and other diseases, these data provide a growing body of evidence that TBL1X is a promising therapeutic target in oncology.
| S-EPMC9929687 | biostudies-literature
Project description: Not available
| S-EPMC7233339 | biostudies-literature
Project description:Immune checkpoint inhibitors (ICI) have significantly improved treatment outcomes for several types of cancer over the past decade, but significant challenges that limit wider effectiveness of current immunotherapies remain to be addressed. Certain "cold" tumor types, such as pancreatic cancer, exhibit very low response rates to ICI due to intrinsically low immunogenicity. In addition, many patients who initially respond to ICI lack a sustained response due to T-cell exhaustion. Several recent studies show that epigenetic modifiers, such as SETDB1 and LSD1, can play critical roles in regulating both tumor cell-intrinsic immunity and T-cell exhaustion. Here, we review the evidence showing that multiple epigenetic regulators silence the expression of endogenous antigens, and their loss induces viral mimicry responses bolstering the response of "cold" tumors to ICI in preclinical models. Similarly, a previously unappreciated role for epigenetic enzymes is emerging in the establishment and maintenance of stem-like T-cell populations that are critical mediators of response to ICI. Targeting the crossroads of epigenetics and immune checkpoint therapy has tremendous potential to improve antitumor immune responses and herald the next generation of sustained responses in immuno-oncology.
| S-EPMC10073242 | biostudies-literature
Project description:BACKGROUND:Psoriasis is a chronic inflammatory multisystem disease with imbalance between the Th17 and T regulatory sub-populations. CD200/CD200R is an anti-inflammatory/immune-suppressive axis that might contribute to its pathogenesis given its relation to the Tregs induction. The current study aimed to investigate the status of the CD200/CD200R axis in the blood of psoriasis vulgaris patients versus healthy controls. METHODS:In this comparative cross sectional study, the blood levels of sCD200 and CD200R levels were measured in 25 psoriasis vulgaris patients and an age and sex matched 25 healthy controls using ELISA and flow-cytometry respectively. Their levels were tested for correlation to disease severity. RESULTS:sCD200 was significantly higher while CD200R was significantly lower in psoriasis vulgaris patients than in controls. They did not correlate to each other or to psoriasis severity although they differed significantly among cases of different severities. CONCLUSION:Aberrant expression of CD200/CD200R might play a role in psoriasis vulgaris pathophysiology and disease severity. It might constitute a future target of therapy, but cannot be used as a marker of disease severity.
| S-EPMC7089552 | biostudies-literature