2B4 and CD48: A powerful couple of the immune system

Pahima, Hadas; Puzzovio, Pier Giorgio; Levi‐Schaffer, Francesca

doi:10.1016/j.clim.2018.10.014

Cited by 32 publications

(22 citation statements)

References 51 publications

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“…The overall (more pronounced) reduction of blood-cell counts observed for several myeloid and lymphoid populations in STAT3mutated vs. WT LGLL cases might be explained by the fact that common surface molecules shared by all the reduced hematopoietic cells could trigger cytotoxicity by clonal LGLs. In this sense, markers such as CD45, CD244, and HLA-I are present or expressed with higher intensity on the surface of neutrophils, eosinophils, dendritic cells, nonclassical monocytes, and NK cells [38][39][40][41][42] which could be potentially recognized by clonal LGLs, and trigger LGL-mediated cytotoxic mechanisms involved in the death/elimination of the target cells. Further studies are needed to confirm which of these or other markers shared by the different leukocyte-cell subsets decreased in T/NK-LGLL patients are potentially targeted by cytotoxic clonal T/NK-LGLs, particularly in STAT3-mutated cases, leading to LGLL-associated cytopenias.…”

Section: Discussionmentioning

confidence: 99%

STAT3 and STAT5B Mutations in T/NK-Cell Chronic Lymphoproliferative Disorders of Large Granular Lymphocytes (LGL): Association with Disease Features

Muñoz-García

Jara‐Acevedo

Caldas

et al. 2020

Cancers

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STAT3 and STAT5B (STAT3/STAT5B) mutations are the most common mutations in T-cell large granular lymphocytic leukemia (T-LGLL) and chronic lymphoproliferative disorders of NK cells (CLPD-NK), but their clinical impact remains unknown. We investigated the frequency and type of STAT3/STAT5B mutations in FACS-sorted populations of expanded T/NK-LGL from 100 (82 clonal; 6 oligoclonal; 12 polyclonal) patients, and its relationship with disease features. Seventeen non-LGL T-CLPD patients and 628 age-matched healthy donors were analyzed as controls. STAT3 (n = 30) and STAT5B (n = 1) mutations were detected in 28/82 clonal T/NK-LGLL patients (34%), while absent (0/18, 0%) among oligoclonal/polyclonal LGL-lymphocytosis. Mutations were found across all diagnostic subgroups: TCD8+-LGLL, 36%; CLPD-NK, 38%; TCD4+-LGLL, 7%; Tαβ+DP-LGLL, 100%; Tαβ+DN-LGLL, 50%; Tγδ+-LGLL, 44%. STAT3-mutated T-LGLL/CLPD-NK showed overall reduced (p < 0.05) blood counts of most normal leukocyte subsets, with a higher rate (vs. nonmutated LGLL) of neutropenia (p = 0.04), severe neutropenia (p = 0.02), and cases requiring treatment (p = 0.0001), together with a shorter time-to-therapy (p = 0.0001), particularly in non-Y640F STAT3-mutated patients. These findings confirm and extend on previous observations about the high prevalence of STAT3 mutations across different subtypes of LGLL, and its association with a more marked decrease of all major blood-cell subsets and a shortened time-to-therapy.

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Section: Discussionmentioning

confidence: 99%

STAT3 and STAT5B Mutations in T/NK-Cell Chronic Lymphoproliferative Disorders of Large Granular Lymphocytes (LGL): Association with Disease Features

Muñoz-García

Jara‐Acevedo

Caldas

et al. 2020

Cancers

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“…This protein is a key cell surface receptor, a member of the signaling lymphocytic activating molecule (SLAM) family, and functions as a receptor in immune regulation (1,2). CD244 mainly binds to the CD48 (another member of the SLAM family) on other immune cells, thus regulating the immune response by a trans interaction (3)(4)(5). In addition to the trans interaction, there is also cis interaction between CD244 and CD48 in NK cells, 2B4/CD48 interaction is essential for the expansion and activation of murine NK cells.…”

Section: Introductionmentioning

confidence: 99%

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

Sun

Gang

et al. 2021

Front. Immunol.

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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.

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“…It is expressed on all NK cells, CD8 + T cells, monocytes, and other immune cells [ 89 ]. 2B4 takes part in NK cell activation and participates in leukocyte differentiation [ 89 , 90 ]. The specific ligand of 2B4 is CD48, which is also a member of CD2 subfamily.…”

Section: Activating Receptorsmentioning

confidence: 99%

Research Progress on NK Cell Receptors and Their Signaling Pathways

Chen

Lü

Чуров

et al. 2020

Mediators of Inflammation

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Natural killer cells (NK cells) play an important role in innate immunity. NK cells recognize self and nonself depending on the balance of activating receptors and inhibitory receptors. After binding to their ligands, NK cell receptors trigger subsequent signaling conduction and then determine whether NK is activated or inhibited. Furthermore, NK cell response includes cytotoxicity and cytokine release, which is tightly related to the activation of NK cell-activating receptors and the inhibition of inhibitory receptors on the surfaces of NK cells. The expression and function of NK cell surface receptors also alter in virus infection, tumor, and autoimmune diseases and influence the occurrence and development of diseases. So, it is important to understand the mechanism of recognition between NK receptors and their ligands in pathological conditions and the signaling pathways of NK cell receptors. This review mainly summarizes the research progress on NK cell surface receptors and their signal pathways.

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2B4 and CD48: A powerful couple of the immune system

Cited by 32 publications

References 51 publications

STAT3 and STAT5B Mutations in T/NK-Cell Chronic Lymphoproliferative Disorders of Large Granular Lymphocytes (LGL): Association with Disease Features

STAT3 and STAT5B Mutations in T/NK-Cell Chronic Lymphoproliferative Disorders of Large Granular Lymphocytes (LGL): Association with Disease Features

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

Research Progress on NK Cell Receptors and Their Signaling Pathways

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