scholarly journals Advances in Understanding the Roles of CD244 (SLAMF4) in Immune Regulation and Associated Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Lin Sun ◽  
Xiaokun Gang ◽  
Zhuo Li ◽  
Xue Zhao ◽  
Tong Zhou ◽  
...  

Proteins in the signaling lymphocytic activating molecule (SLAM) family play crucial roles in regulating the immune system. CD244 (SLAMF4) is a protein in this family, and is also a member of the CD2 subset of the immunoglobulin (Ig) superfamily. CD244 is a cell surface protein expressed by NK cells, T cells, monocytes, eosinophils, myeloid-derived suppressor cells, and dendritic cells. CD244 binds to the ligand CD48 on adjacent cells and transmits stimulatory or inhibitory signals that regulate immune function. In-depth studies reported that CD244 functions in many immune-related diseases, such as autoimmune diseases, infectious diseases, and cancers, and its action is essential for the onset and progression of these diseases. The discovery of these essential roles of CD244 suggests it has potential as a prognostic indicator or therapeutic target. This review describes the molecular structure and function of CD244 and its roles in various immune cells and immune-related diseases.

Development ◽  
1987 ◽  
Vol 101 (2) ◽  
pp. 255-265 ◽  
Author(s):  
J.A. Anstrom ◽  
J.E. Chin ◽  
D.S. Leaf ◽  
A.L. Parks ◽  
R.A. Raff

In this report, we use a monoclonal antibody (B2C2) and antibodies against a fusion protein (Leaf et al. 1987) to characterize msp130, a cell surface protein specific to the primary mesenchyme cells of the sea urchin embryo. This protein first appears on the surface of these cells upon ingression into the blastocoel. Immunoelectronmicroscopy shows that msp130 is present in the trans side of the Golgi apparatus and on the extracellular surface of primary mesenchyme cells. Four precursor proteins to msp130 are identified and we show that B2C2 recognizes only the mature form of msp130. We demonstrate that msp130 contains N-linked carbohydrate groups and that the B2C2 epitope is sensitive to endoglycosidase F digestion. Evidence that msp130 is apparently a sulphated glycoprotein is presented. The recognition of the B2C2 epitope of msp130 is disrupted when embryos are cultured in sulphate-free sea water. In addition, two-dimensional immunoblots show that msp130 is an acidic protein that becomes substantially less acidic in the absence of sulphate. We also show that two other independently derived monoclonal antibodies, IG8 (McClay et al. 1983; McClay, Matranga & Wessel, 1985) and 1223 (Carson et al. 1985), recognize msp130, and suggest this protein to be a major cell surface antigen of primary mesenchyme cells.


2019 ◽  
Vol 445 (1) ◽  
pp. 16-28 ◽  
Author(s):  
Yanina-Yasmin Pesch ◽  
Ricarda Hesse ◽  
Tariq Ali ◽  
Matthias Behr

2020 ◽  
Vol 69 (11) ◽  
pp. 2233-2245
Author(s):  
Mohammed L. Ibrahim ◽  
Chunwan Lu ◽  
John D. Klement ◽  
Priscilla S. Redd ◽  
Dafeng Yang ◽  
...  

2016 ◽  
Vol 130 (16) ◽  
pp. 1453-1467 ◽  
Author(s):  
Jianjian Ji ◽  
Jingjing Xu ◽  
Shuli Zhao ◽  
Fei Liu ◽  
Jingjing Qi ◽  
...  

Although major advancements have made in investigating the aetiology of SLE (systemic lupus erythaematosus), the role of MDSCs (myeloid-derived suppressor cells) in SLE progression remains confused. Recently, some studies have revealed that MDSCs play an important role in lupus mice. However, the proportion and function of MDSCs in lupus mice and SLE patients are still poorly understood. In the present study, we investigated the proportion and function of MDSCs using different stages of MRL/lpr lupus mice and specimens from SLE patients with different activity. Results showed that splenic granulocytic (G-)MDSCs were significantly expanded by increasing the expression of CCR1 (CC chemokine receptor 1) in diseased MRL/lpr lupus mice and in high-disease-activity SLE patients. However, the proportion of monocytic (M-)MDSCs remains similar in MRL/lpr lupus mice and SLE patients. G-MDSCs produce high levels of ROS (reactive oxygen species) through increasing gp91phox expression, and activated TLR2 (Toll-like receptor 2) and AIM2 (absent in melanoma 2) inflammasome in M-MDSCs lead to IL-1β (interleukin 1β) expression in diseased MRL/lpr mice and high-disease-activity SLE patients. Previous study has revealed that MDSCs could alter the plasticity of Th17 (T helper 17) cells and Tregs (regulatory T-cells) via ROS and IL-1β. Co-culture experiments showed that G-MDSCs impaired Treg differentiation via ROS and M-MDSCs promoted Th17 cell polarization by IL-1β in vitro. Furthermore, adoptive transfer or antibody depletion of MDSCs in MRL/lpr mice confirmed that MDSCs influenced the imbalance of Tregs and Th17 cells in vivo. Our results indicate that MDSCs with the capacity to regulate Th17 cell/Treg balance may be a critical pathogenic factor in SLE.


2016 ◽  
Author(s):  
Andrew R. Stiff ◽  
Prashant Trikha ◽  
Robert Wesolowski ◽  
Kari Kendra ◽  
Sarvani Uppati ◽  
...  

2019 ◽  
Vol 122 (1) ◽  
pp. 23-29 ◽  
Author(s):  
Cong Hu ◽  
Bo Pang ◽  
Guangzhu Lin ◽  
Yu Zhen ◽  
Huanfa Yi

AbstractIn recent years, a large number of studies have been carried out in the field of immune metabolism, highlighting the role of metabolic energy reprogramming in altering the function of immune cells. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells generated during a large array of pathological conditions, such as cancer, inflammation, and infection, and show remarkable ability to suppress T-cell responses. These cells can also change their metabolic pathways in response to various pathogen-derived or inflammatory signals. In this review, we focus on the roles of glucose, fatty acid (FA), and amino acid (AA) metabolism in the differentiation and function of MDSCs in the tumour microenvironment, highlighting their potential as targets to inhibit tumour growth and enhance tumour immune surveillance by the host. We further highlight the remaining gaps in knowledge concerning the mechanisms determining the plasticity of MDSCs in different environments and their specific responses in the tumour environment. Therefore, this review should motivate further research in the field of metabolomics to identify the metabolic pathways driving the enhancement of MDSCs in order to effectively target their ability to promote tumour development and progression.


2010 ◽  
Vol 3 ◽  
pp. CMENT.S3147
Author(s):  
Kamal-Eldin Ahmed Abou-Elhamd

Apoptosis is an active process of programmed cell death. Fas is a cell-surface protein which is expressed on activated lymphocytes and known as CD95, TNFRSF6 or APO-1. Fas-L is ligand of Fas and known as CD95 LG or TNFSF6. Apoptosis or cell death is a result of binding of Fas-L to Fas which is expressed on the surfaces of these cells. Cancer cells escape this binding by overexpression of Fas-L or down expression of Fas. Fas and Fas-L exist in membrane bound and soluble forms. The serum level of sFas and sFas-L can be evaluated by immunostaining, immunohistochemical methods, immunofluorescence, flow cytometry and Western blotting. Head and neck squamous cell carcinoma diagnosis, staging and prognosis can be evaluated early and accurately by sFas and sFas-L expression levels detection.


2018 ◽  
Vol 115 (46) ◽  
pp. E10988-E10997 ◽  
Author(s):  
Damaris Bausch-Fluck ◽  
Ulrich Goldmann ◽  
Sebastian Müller ◽  
Marc van Oostrum ◽  
Maik Müller ◽  
...  

Cell-surface proteins are of great biomedical importance, as demonstrated by the fact that 66% of approved human drugs listed in the DrugBank database target a cell-surface protein. Despite this biomedical relevance, there has been no comprehensive assessment of the human surfaceome, and only a fraction of the predicted 5,000 human transmembrane proteins have been shown to be located at the plasma membrane. To enable analysis of the human surfaceome, we developed the surfaceome predictor SURFY, based on machine learning. As a training set, we used experimentally verified high-confidence cell-surface proteins from the Cell Surface Protein Atlas (CSPA) and trained a random forest classifier on 131 features per protein and, specifically, per topological domain. SURFY was used to predict a human surfaceome of 2,886 proteins with an accuracy of 93.5%, which shows excellent overlap with known cell-surface protein classes (i.e., receptors). In deposited mRNA data, we found that between 543 and 1,100 surfaceome genes were expressed in cancer cell lines and maximally 1,700 surfaceome genes were expressed in embryonic stem cells and derivative lines. Thus, the surfaceome diversity depends on cell type and appears to be more dynamic than the nonsurface proteome. To make the predicted surfaceome readily accessible to the research community, we provide visualization tools for intuitive interrogation (wlab.ethz.ch/surfaceome). The in silico surfaceome enables the filtering of data generated by multiomics screens and supports the elucidation of the surfaceome nanoscale organization.


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