Hyaluronidase 2-expressing splenic Z cell (Z cell)

Hyal2+ CD3- CD19- splenic Z cells are a novel population of innate-like lymphoid cells characterized by the expression of Hyaluronidase 2 (Hyal2) and the absence of traditional T-cell (CD3) and B-cell (CD19) markers (Oncotarget, 2015; Frontiers, 2015). These cells are primarily localized in the spleen and are activated by the synthetic peptide Zfra (zinc finger-like protein that regulates apoptosis) through its binding to membrane-anchored Hyal2, which acts as a cognate receptor (Oncotarget, 2015; IJMS, 2024). Upon activation, Z cells undergo clonal expansion and can mount a potent, antigen-independent memory anticancer response, effectively suppressing tumor growth, metastasis, and stemness in various cancer models (Oncotarget, 2015; Cancers, 2020). Beyond oncology, activated Z cells have shown potential in retarding neurodegeneration, such as in Alzheimer's disease, by migrating to the brain and modulating inflammatory pathways like NF-κB (IJMS, 2024). Their unique ability to provide broad-spectrum protection without prior exposure to specific cancer antigens makes them a promising target for cell-based immunotherapies and peptide-mediated immune modulation (Oncotarget, 2015; Frontiers, 2015).

Other names

Hyal2+ CD3- CD19- Z lymphocyteZfra-binding cellNon-T/non-B splenic lymphocyteSplenic Z cell

Activation of the Hyal-2/WWOX/SMAD4 signaling pathway via Zfra peptide binding to membrane-anchored Hyaluronidase 2, leading to clonal expansion and relocation of cytotoxic Z cells to disease sites.