| 2019 |
MS4A4A physically interacts and colocalizes with the β-glucan receptor dectin-1 in lipid rafts of macrophages; Ms4a4a-deficient macrophages show defective dectin-1 signaling and defective production of effector molecules in response to dectin-1 ligands, placing MS4A4A upstream of dectin-1-dependent activation and NK cell-mediated metastasis control. |
Co-localization/interaction studies in lipid rafts, Ms4a4a-deficient macrophage functional assays (signaling readouts, effector molecule production), in vivo tumor metastasis models with genetic knockout |
Nature immunology |
High |
31263276
|
| 2020 |
In human mast cells, MS4A4A promotes phosphorylation of PLCγ1, calcium flux, and degranulation in response to IgE-mediated FcεRI crosslinking; MS4A4A interacts with caveolin-1 and facilitates recruitment of FcεRI and KIT into lipid rafts; MS4A4A also regulates Orai1-mediated store-operated Ca2+ entry (SOCE) downstream of Ca2+ store release. |
siRNA knockdown in human mast cells, phosphorylation assays (western blot), calcium flux measurements, degranulation assays, co-immunoprecipitation with caveolin-1, lipid raft fractionation |
Cellular signalling |
High |
32240745
|
| 2020 |
MS4A4A regulates expression of arginase 1 in macrophages under IL-4 stimulation and regulates eosinophil infiltration during lung allergic inflammation (house dust mite model) in mice. |
Ms4a4a-deficient mice, in vitro macrophage stimulation with IL-4, in vivo intranasal house dust mite challenge model with cellular readouts |
European journal of immunology |
Medium |
32589266
|
| 2023 |
MS4A4A promotes M2 polarization of macrophages by activating the PI3K/AKT and JAK/STAT6 signaling pathways; MS4A4A blockade in vivo reshapes the tumor immune microenvironment by reducing M2-TAM infiltration and increasing effector CD8+ T-cell infiltration. |
RNA sequencing, western blot analysis, flow cytometry, in vivo murine subcutaneous and orthotopic tumor models with MS4A4A inhibition and anti-MS4A4A monoclonal antibody treatment |
Gut |
Medium |
37507218
|
| 2025 |
MS4A4A interacts with MS4A6A and protects it from degradation; MS4A6A in turn forms a complex with and blocks the co-receptor DAP12, which modulates levels and signaling of TREM2 and other receptors; thereby MS4A4A and MS4A6A cooperatively act as post-transcriptional negative regulators of both transmembrane and soluble TREM2 and of microglial viability, phagocytosis, and lysosomal function. |
CRISPR knockout and overexpression of MS4A4A in macrophages/microglia, MS4A4A-degrading antibodies, co-immunoprecipitation (MS4A4A–MS4A6A and MS4A6A–DAP12 complexes), non-human primate and mouse amyloid pathology models, flow cytometry, functional phagocytosis/lysosomal assays |
Neuron |
High |
41435829
|
| 2025 |
Ms4a4a deletion in a 5xFAD mouse model reduces steady-state amyloid-β levels, shortens Aβ half-life in brain interstitial fluid, increases plaque compaction, and reduces overall plaque burden; microglia lacking Ms4a4a are more pro-inflammatory and produce elevated MMP-9, which may facilitate Aβ degradation. |
Ms4a4a knockout in 5xFAD mice, brain interstitial fluid Aβ half-life measurement, plaque burden quantification, microglial inflammatory profiling, MMP-9 measurement (mouse and human CSF) |
Alzheimer's & dementia |
Medium |
40843775
|
| 2025 |
Ms4a4a deletion impairs microglial phagocytosis, diminishes calcium influx, and disrupts mitochondrial metabolic fitness; the cytosolic fragment of Ms4a4a is anchored to cytoskeletal components, supporting its role in mediating phagocytosis; induction of Ms4a4a via central LNP-Il4 delivery alleviates seizure conditions in an AD mouse model. |
Ms4a4a knockout mouse model, microglial phagocytosis assays, calcium influx measurements, mitochondrial metabolic assays, cytoskeletal anchoring experiments, in vivo LNP-IL-4 delivery with seizure readout |
Advanced science |
Medium |
40349168
|
| 2025 |
In a mouse model of arthritis, Ms4a4a deletion does not alter disease course but is associated with enhanced therapeutic response specifically to corticosteroids; corticosteroids enhance expression of MS4A4A and FcγR3 in macrophages in vitro and in vivo, suggesting MS4A4A upregulation by corticosteroids counteracts their therapeutic activity. |
Ms4a4a-deficient mice in experimental arthritis model, in vitro corticosteroid treatment of human and murine macrophages, immunohistochemistry, RNA sequencing |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
40924449
|
| 2026 |
MS4A4A regulates macrophage M2 polarization through NF-κB and JAK-STAT6 signaling pathways; macrophages overexpressing MS4A4A promote glioma cell proliferation, invasion, and temozolomide resistance in vitro and in vivo; targeting the MS4A4A/NF-κB/STAT6 axis improves outcomes in a glioma mouse model. |
MS4A4A knockdown and overexpression in macrophages, western blot for NF-κB and STAT6 pathway components, co-culture invasion/proliferation assays, in vivo subcutaneous and orthotopic glioma mouse models |
Oncogene |
Medium |
42056558
|
| 2017 |
MS4A4A protein is localized to the plasma membrane in monocytes; it is expressed in M2 (IL-4-polarized) macrophages but not M1 (IFN-γ/LPS-activated) macrophages; it is induced during monocyte-to-macrophage differentiation and absent in immature/precursor myeloid cells and healthy B lymphocytes but present in plasma cells. |
Monoclonal antibody generation against extracellular epitopes, flow cytometry of human peripheral blood, in vitro monocyte differentiation assays |
Immunology and cell biology |
Medium |
28303902
|