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Putative functions of CD31 in the regulation of the immune system. (1) In the thymus, CD31 interactions might affect the positive and negative selection of thymocytes by regulating TCR signaling. (2) In mature naı¨venaı¨ve T-cells, CD31 contributes to the regulation of homeostatic expansion and facilitates their access to lymphoid organs. (3) T-cell expansion and survival following activation are also regulated by CD31-mediated interactions with DCs; these interactions, in turn, protect DCs from cytolytic killing. CD31-CD31 interactions might also be important to control the expansion of antigen-specific B-cells that are stimulated by T-cells and/or dendritic cells bearing antibody-antigen immune complexes. (4) Finally, activation-induced natural killer (NK)-mediated cell lysis of T-and B-lymphocytes and of dendritic cells might also be regulated by CD31-CD31 interactions between these immune cells. BCR, B-cell receptor; HEV, high endothelial venule; LEC, lymphatic endothelial cell; MHC, major histocompatibility complex; TCR, T-cell receptor.
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Although it is expressed by all leukocytes, including T-, B-lymphocytes and dendritic cells, the immunoglobulin-like receptor CD31 is generally regarded by immunologists as a marker of endothelial cell lineage that lacks an established functional role in adaptive immunity. This perception has recently been challenged by studies that reveal a key ro...
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Citations
... Prolactin (Prl) was the only other factor that fit this criterion [12,13], and placenta has been reported to be an extra-pituitary site for the synthesis of this hormone [14]. Lastly, Cd31/Pecam1, which is often used as a marker of endothelial cell lineage [15] was also included. ...
Heme oxygenase 1 (Hmox1), the inducible form of heme degrading enzymes Hmoxs, is important for establishment and maintenance of pregnancy. A growing body of evidence suggests an association between Hmox1 and angiogenesis, including placental angiogenesis. In this study, we examined the expression of two angiogenic factors in the placentas of Hmox1 deficient mouse embryos, whose expression was found to be related to that of Hmox1. Relative protein levels and localization of Hmoxs and two angiogenic factors [Vegf and Prolactin along with their receptors, and Cd31/Pecam1] were compared in the placentas of Hmox1 wildtype and knockout mouse embryos using western blotting and immunohistochemistry along with histological analysis. The results revealed tissue disorganisation, reduced area of labyrinth and smaller nuclear size of trophoblast giant cell in the placentas of knockout embryos. The levels of Hmox2, prolactin, and Cd31/Pecam1 were found to be altered in knockout placentas, whereas Vegf and its receptors seem to be unaltered in our samples. Overall, our findings imply that Hmox2 is unlikely to compensate for Hmox1 deficiency in knockout placentas, and altered levels of prolactin and Cd31/Pecam1 hint towards impaired angiogenesis in these placentas. Further investigation would be needed to understand the molecular mechanism of defective angiogenesis in the placentas of Hmox1 knockout mouse embryos.
... CD31 is an immunoglobulin (Ig)-like protein known to act as a co-inhibitory receptor on lymphocytes due to the presence of two immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in its cytoplasmic tail. Upon phosphorylation, CD31 ITIMs become docking sites for Src Homology 2 (SH2)-containing phosphatases, uncoupling ITAM-dependent leukocyte activation (Henshall et al., 2001;Marelli-Berg et al., 2013). Being expressed by all hematopoietic cells and ECs, CD31 ITIM signaling properties confer a pleiotropic and central role to CD31 in maintaining homeostasis at the blood-vessel interface (Caligiuri, 2020). ...
Effective neutrophil migration to sites of inflammation is crucial for host immunity. A coordinated cascade of steps allows intravascular leukocytes to counteract the shear stress, transmigrate through the endothelial layer and move towards the extravascular, static environment. Those events are tightly orchestrated by integrins but, while the molecular mechanisms leading to their activation have been characterized, the regulatory pathways promoting their detachment remain elusive. In light of this, it has long been known that Platelet-Endothelial Cell Adhesion Molecule ( Pecam1 , also known as CD31) deficiency blocks leukocyte transmigration at the level of the outer vessel wall, yet the associated cellular defects are controversial. In this study, we combined an unbiased proteomic study with in vitro and in vivo single-cell tracking in mice to study the dynamics and role of CD31 during neutrophil migration. We found that CD31 localizes to the uropod of migrating neutrophils along with closed β 2 -integrin and is required for essential neutrophil actin/integrin polarization. Accordingly, the uropod of Pecam1 -/- neutrophils is unable to detach from the extracellular matrix, while antagonizing integrin binding to extracellular matrix components rescues this in vivo migratory defect. Conversely, we showed that sustaining CD31 co-signaling actively favors uropod detachment and effective migration of extravasated neutrophils to sites of inflammation in vivo . Altogether, our results suggest that CD31 acts as a molecular rheostat controlling integrin-mediated adhesion at the uropod of egressed neutrophils thereby triggering their detachment from the outer vessel wall to reach the inflammatory sites.
... CD31 is a co-modulator of T cell immunity, involved in leukocyte-leukocyte interactions, as well as in interactions between lymphocytes and the vascular endothelium, leukocyte extravasation, and migration to the inflamed tissues through intercellular junctions. CD31 plays a role in the regulation of vascular stability [29][30][31]. In CD4+ T lymphocytes, CD31+ is expressed in naïve recent thymic emigrants but is downregulated after acute T cell activation and absent from memory cells. ...
... We studied CD31 expression on well-defined cells, T lymphocytes. It is known that CD31 expression is reduced by shedding in activated T cells and CD31 is possibly associated with T cell subsets with an immunosuppressive function [30]. Our results regarding the possible prognostic role of the low CD31+ marker expression in blood CD4+ T cells together with the high expression on BALF CD8+ T cells appear to be in indirect agreement with the results of other studies regarding CD31. ...
The search for biological markers, which allow a relatively accurate assessment of the individual course of pulmonary sarcoidosis at the time of diagnosis, remains one of the research priorities in this field of pulmonary medicine. The aim of our study was to investigate possible prognostic factors for pulmonary sarcoidosis with a special focus on cellular immune inflammation markers. A 2-year follow-up of the study population after the initial prospective and simultaneous analysis of lymphocyte activation markers expression in the blood, as well as bronchoalveolar lavage fluid (BALF) and lung biopsy tissue of patients with newly diagnosed pulmonary sarcoidosis, was performed. We found that some blood and BAL fluid immunological markers and lung computed tomography (CT) patterns have been associated with a different course of sarcoidosis. We revealed five markers that had a significant negative association with the course of sarcoidosis (worsening pulmonary function tests and/or the chest CT changes)—blood CD4+CD31+ and CD4+CD44+ T lymphocytes, BALF CD8+CD31+ and CD8+CD103+ T lymphocytes and a number of lung nodules on chest CT at the time of the diagnosis. Cut-off values, sensitivity, specificity and odds ratio for predictors of sarcoidosis progression were calculated. These markers may be reasonable predictors of sarcoidosis progression.
... In general, sEV from patients and controls expressed similarly the molecules found on platelets with the possible exception for CD63 and CD62P, which are characteristic of activated platelet sEV and were reduced in active RA (Figure 11g, h) (Heijnen et al., 1999). Finally, the classical endothelial cell marker, CD31, which is also expressed on leukocytes and platelets and that is critical for adhesion and transmigration, was less abundant in all the patient groups, which is interesting because decreased CD31 is associated with excessive immunoreactivity (Figure 11j) (Marelli-Berg et al., 2013). Collectively the results identify consistent differences in protein expression patterns in sEV purified from fresh PPP between the patients and healthy controls in our cohorts, which are likely to reflect real differences in circulating sEV. ...
Small extracellular vesicles (sEV) purified from blood have great potential clinically as biomarkers for systemic disease; however interpretation is complicated by release of sEV ex vivo after blood taking. To quantify the problem and devise ways to minimise it, we characterised sEV in paired serum, plasma and platelet poor plasma (PPP) samples from healthy donors. Immunoblotting showed twofold greater abundance of CD9 in sEV fractions from fresh serum than from fresh plasma or PPP. MACSPlex confirmed this, and showed that proteins expressed on platelet sEV, either exclusively (CD41b, CD42a and CD62P) or more widely (HLA-ABC, CD24, CD29 and CD31) were also twofold more abundant; by contrast non-platelet proteins (including CD81) were no different. Storage of plasma (but not serum) increased abundance of platelet and selected leukocyte sEV proteins to at least that of serum, and this could be recapitulated by activating cells in fresh plasma by Ca2+, an effect abrogated in PPP. This suggests that a substantial proportion of sEV in serum and stored plasma were generated ex vivo, which is not the case for fresh plasma or PPP. Thus we provide strategies to minimise ex vivo sEV generation and criteria for identifying those that were present in vivo.
... In this study, we showed decrease of CD69 expression on sEVs at 1% CSE, suggesting reduced activation of cells producing EVs after exposure to 1% CSE. Furthermore, CD31 is an endothelial cell adhesion molecule expressed by vascular endothelial cells platelets and leukocytes [73,74] and is thought to have a function in downregulating T-cell activation [74,75]. In this study, EV expression of CD31 decreased at 1% CSE concentration compared to control and 3% CSE concentration. ...
Extracellular vesicles (EVs) function as mediators of intercellular communication and as such influence the recipient cell function. EVs derived from immune cells can carry out many of the same functions as their parental cells, as they carry costimulatory molecules, antigens, and antigen-MHC complexes. As a result, there is a strong interest in understanding the composition and origin of immune cell derived EVs in order to understand their role in the pathogenesis of diseases. This study aimed to optimise methodologies to study immune cell derived EVs. Peripheral blood mononuclear cell-derived small EVs (sEVs) were isolated and observed using conventional transmission electron microscopy (TEM) and sized by nanoparticle tracking analysis (NTA). They were then enumerated and profiled using Imaging Flow Cytometry (IFC) and were further characterised using a flow cytometric multiplex bead assay. These techniques were then applied to our current research, namely smoking-related inflammatory disease. We present here a comprehensive approach to analyse PBMC-derived sEVs in smoking-related inflammatory disease following the Minimal Information for Studies of Extracellular Vesicle (MISEV) 2018 guidelines. This article is protected by copyright. All rights reserved.
... CD31 acts in angiogenesis, detachment of leukocytes, stimulation of lymphocytes, and stimulation of platelets (8). CD31 is a platelet endothelial cell adhesion molecule 1 (PECAM-1), which has a receptor on endothelial cells (9). In this study, we evaluated blood and lymphatic vessels for IRANIAN JOURNAL OF PATHOLOGY CD31 expression on endothelial cells. ...
Background & objective:
Lymphovascular tumoral invasion is a typical histopathological feature of gastric carcinomas and supports the recognition of high-risk patients for the recurrence. We aimed to study CD31 expression in diverse subtypes of gastric carcinomas and to show its association with the histopathologic findings of the carcinoma to assess the prognosis.
Methods:
This cross-sectional study was conducted on 40 established patients with gastric adenocarcinoma from radical gastrectomy. The patients were classified according to the pathology assessments. Tumoral tissues were assessed by immunohistochemical staining for CD31 expression. Malignant behavior was estimated by histopathological evaluations.
Results:
CD31 positivity was described in 23 (57.5%) of all evaluated patients. In assessment of CD31 expression and tumor features presented, no significant association between the CD31 expression and patients' age, sex, tumor site, size, grade and stage, subtypes of carcinoma, perineural invasion, and also lymphovascular invasion was found. (P>0.05).
Conclusion:
Lymphovascular invasion may make valuable additional evidence and may be useful to detect gastric carcinoma patients at high risk for recurrence, who could be candidates for more supplementary therapies. However, in our study, CD31 expression did not show any association with the aggressive histopathologic features of this tumor.
... Skin graft rejection by CD31 −/− females was significantly accelerated and more pronounced than that of wild-type females 70 . CD31 plays a complex role in the regulation of T-cell-mediated immune responses 71 . One of the most studied roles of CD31 is its ability to inhibit the protein tyrosine kinasedependent signal transduction mediated by the immunoreceptor tyrosine-based activation motif-containing T-cell receptor 72 . ...
We evaluated the contribution of artificial intelligence in predicting the risk of acute cellular rejection (ACR) using early plasma levels of soluble CD31 (sCD31) in combination with recipient haematosis, which was measured by the ratio of arterial oxygen partial pressure to fractional oxygen inspired (PaO 2 /FiO 2 ) and respiratory SOFA (Sequential Organ Failure Assessment) within 3 days of lung transplantation (LTx). CD31 is expressed on endothelial cells, leukocytes and platelets and acts as a “peace-maker” at the blood/vessel interface. Upon nonspecific activation, CD31 can be cleaved, released, and detected in the plasma (sCD31). The study included 40 lung transplant recipients, seven (17.5%) of whom experienced ACR. We modelled the plasma levels of sCD31 as a nonlinear dependent variable of the PaO 2 /FiO 2 and respiratory SOFA over time using multivariate and multimodal models. A deep convolutional network classified the time series models of each individual associated with the risk of ACR to each individual in the cohort.
... The appearance of inflammatory cells, blood vessels, and fibrosis may be evidence of a more advanced lesion. CD31 expression was found in some cells without obvious blood vessels or lumen [19]. As CD31 can be expressed both by endothelial cells and leukocytes, the observed cells might either be primary endothelial cells or leukocytes. ...
Purpose
To investigate the pathogenic features of the polypoidal lesions from the specimens of polypoidal choroidal vasculopathy extracted from human subjects.
Methods
Seven specimens of polypoidal lesions extracted from five eyes of six patients (mean age, 60.16 ± 10.41 years) of polypoidal choroidal vasculopathy were examined. The polypoidal lesions were obtained by surgical excision. Thereafter, a histopathological analysis of the specimens was performed.
Results
The polypoidal lesions were oval nodules located underneath the retinal pigment epithelium. A pathological study of the lesions revealed that Bruch’s membrane schisis was observed in all specimens and they were all located in the Bruch’s membrane. The Bruch’s membrane schisis and serosanguineous materials constituted the main structure of the lesions in five of the seven specimens, with small vessels being observed in two specimens. One specimen was composed of two polypoidal lesions of different characteristics, and one specimen had a neovessel membrane complex with several polypoidal lesions. Inflammatory cells and blood vessels were observed in the polypoidal lesion of the specimen with neovessel membrane complex.
Conclusion
Polypoidal lesions of polypoidal choroidal vasculopathy are abnormalities of the Bruch’s membrane. The lesions are characterized by the Bruch’s membrane schisis, which is filled with serosanguineous materials. The lesions are progressive and may contain inflammatory cells and blood vessels.
... PECAM-1 seems to control the activation of T cells in order to prevent AICD (activation-induced cell death) due to overstimulation [36]. PECAM-1 cytoplasmic domain with ITIM motifs is phosphorylated after TCR-mediated activation, protein-tyrosine phosphatases are then recruited and eventually, TCR signalling is inhibited [37]. Moreover, PECAM-1 is known to be preferentially expressed by naive Th cells [38]. ...
... Moreover, PECAM-1 is known to be preferentially expressed by naive Th cells [38]. In several autoimmune murine models, including experimental autoimmune encephalomyelitis, PECAM-1-deficiency leads to a more severe disease course [37]. Furthermore, an increased level of soluble PECAM-1 was observed among MS patients [23,24]. ...
Introduction. PECAM-1 and NKRP1A are both involved in the vascular transmigration of T lymphocytes. Vascular transmigration is a crucial process in multiple sclerosis pathogenesis. Methods and aim. The current paper presents an analysis of PECAM-1 and NKRP1A expression on γδ T cells. Expression of PECAM-1 and NKRP1A on subsets of γδ T cells was performed with flow cytometry. Results. Based on the flow cytometry data, PECAM1 was slightly differentially modulated on γδ T cells—it was up-regulated during relapse, but down-regulated during remission. Moreover, a significant downregulation of CD3 expression was noted on γδ T cells from MS patients, most notably during relapse. Conclusions. This may be a sign of the overall activation of γδ T cells in the course of multiple sclerosis
... It can be hypothesized that some of these activated Treg cells in the PBMC population of human blood are mTregs that persist in the absence of antigenic stimulation. Resting CD45RA + FOXP3 low Treg cells of umbilical cord blood express CD31, indicating recent emigration from the thymus [114][115][116][117]. Meanwhile, some conventional effector T cells that are recent thymic emigrants are known to undergo peripheral post-thymic proliferation giving rise to a longlived memory T-cell population that can maintain a naïve pool of T cells in the elderly [114]. ...
In immunology, the discovery of regulatory T (Treg) cells was a major breakthrough. Treg cells play a key role in pregnancy maintenance, in the prevention of autoimmune responses, and in the control of all immune responses, including responses to self cells, cancer, infection, and a transplant. It is currently unclear whether Treg cells are capable of long-term memory of an encounter with an antigen. Although the term “immunological memory” usually means an enhanced ability to protect the body from reinfection, the memory of the suppressive activity of Treg cells helps to avoid the state of generalized immunosuppression that may result from the second activation of the immune system. In this review, we would like to discuss the concept of regulatory memory and in which tissues memory Treg cells can perform their functions.
