Biology subjects

Kizilirmak, A. B.

Publications and source records attributed to Kizilirmak, A. B..

3 recordsLinked to original sources

bioRxiv2026

CD8+CD20+ Cytotoxic T Lymphocytes Exhibit Augmented Degranulation and Pro-inflammatory Potential in Multiple Sclerosis

The effectiveness of CD20-targeting therapies in multiple sclerosis (MS) underscores the role of B cells in the disease, yet the limited success of other B cell-specific treatments suggests additional mechanisms at play. Intriguingly, CD20 is also expressed on a subset of highly active memory T cells, particularly cytotoxic CD8+ T lymphocytes (CTLs). This study investigated the functional characteristics of CD8+CD20+ CTLs in MS. We observed a significant increase in CD8+CD20+ CTL prevalence in MS patients, with enhanced infiltration into the cerebrospinal fluid. Consistent with prior reports, these cells exhibited heightened proliferation and production of IFN-{gamma}, TNF-, and GM-CSF. Notably, we demonstrate for the first time that CD8+CD20+ CTLs display escalated degranulation and produce significantly higher levels of Granzyme B, Perforin, and Granzyme K compared to their CD20-counterparts, with further augmentation in pwMS compared to healthy controls. These findings suggest that in MS, CD8+CD20+ CTLs are actively recruited to the CNS, exhibiting enhanced cytotoxicity and a potent pro-inflammatory profile, particularly through elevated Granzyme K production, contributing significantly to the chronic inflammatory milieu and immunopathogenesis of MS.

immunology↗

bioRxiv2025

CD20+ natural killer cells are polyfunctional, memory-like cells that are enriched in inflammatory disorders

While CD20 was initially characterized as a B cell-specific marker, its expression on memory T cells has expanded our understanding of this molecules distribution and function. Here, we identify a previously unrecognized CD20-expressing NK cell population and demonstrate its functional significance. CD56+CD20+ NK cells exhibit hallmarks of cellular activation, including elevated NKp46, CD69, and CD137 expression, enhanced proliferative capacity, and increased production of inflammatory cytokines (IFN-{gamma}, GM-CSF, TNF-, IL-10). Functional analyses revealed enhanced cytotoxicity against K562 targets, correlating with increased expression of cytolytic mediators including granzymes A, B, and K, perforin, FASL, and TRAIL. Single-cell transcriptional profiling demonstrated that MS4A1-expressing NK cells possess a distinct molecular signature characterized by elevated granzyme K expression and memory-like features. These cells preferentially localize to secondary lymphoid organs and accumulate in inflammatory tissues. Notably, CD56+CD20+ NK cells are enriched in multiple inflammatory conditions, including multiple sclerosis, autoimmune hepatitis, hepatitis B infection, hepatocellular carcinoma, and lung cancer. Treatment with rituximab depletes this population, suggesting potential therapeutic implications. Our findings establish CD20+ NK cells as a functionally distinct lymphocyte subset with enhanced effector capabilities and tissue-homing properties, providing new insights into immune regulation in inflammatory diseases. One Sentence SummaryOur study reveals expression of CD20 by NK cells, in relation with enhanced functionality, memory-like features, and inflammation.

immunology↗

bioRxiv2024

A Novel Mouse Model Demonstrates In Vivo Replenishment of Central Nervous System Pericytes After Successful Acute Ablation

Central nervous system (CNS) pericytes play crucial roles in vascular development and blood-brain barrier maturation during prenatal development, as well as in regulating cerebral blood flow in adults. They have also been implicated in the pathogenesis of numerous neurological disorders. However, the behavior of pericytes in the adult brain after injury remains poorly understood, partly due to limitations in existing pericyte ablation models. To investigate pericyte responses following acute ablation, we developed a tamoxifen-inducible pericyte ablation model by crossing PDGFR{beta}-P2A-CreERT2 and Rosa26-DTA176 transgenic mouse lines. Using this model, we studied the effects of different tamoxifen doses and conducted histological examinations 15 and 60 days post-injection to assess both short- and long-term impacts of pericyte ablation. Our results demonstrate that a low dose of tamoxifen effectively ablates CNS pericytes in mice without reducing survival or causing significant systemic side effects, such as weight loss. Additionally, we found that the extent of pericyte depletion varies between the cortex and the spinal cords gray and white matter regions. Importantly, both pericyte coverage and numbers increased in the weeks following acute ablation, indicating the regenerative capacity of CNS pericytes in vivo. This model offers a valuable tool for future studies on the role of pericytes in neurological disorders, overcoming the limitations of constitutive pericyte ablation models.

neuroscience↗