Biology subjects

Doran, T.

Publications and source records attributed to Doran, T..

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↗

bioRxiv2019

Generation of transgenic quails by in vivo transfection of primordial germ cells

During development, dynamic changes in tissue shapes known as morphogenesis result from the exquisite orchestration of signalling pathways, cell-cell interactions, cell divisions, and coordinated movements. How cells within embryos adopt a vast array of cell fates and tissue shapes in such an ever-changing environment has fascinated scientists for generations, yet the ability to observe and characterize those rapid changes has proven technically challenging in higher vertebrates. The japanese quail (Coturnix coturnix japonica) is an attractive model where basic rules driving morphogenesis in amniotes can be deciphered using genetic approaches. Similar to the more popular chicken model, the quail embryo is easily accessible to a wide range of manipulations and live imaging. A decisive asset of quail over chicken is a much shorter life cycle, which makes its use as genetic model for basic research extremely appealing. To date, all existing transgenic quail lines were generated using replication-deficient lentiviruses, but diverse limitations of this approach have hindered the widespread expansion of such technology. Here, we successfully used a plasmid-based in vivo transfection of quail primordial germ cells (PGCs) to generate a number of transgenic quail lines over a short period of time. The plasmid-based approach is simple, efficient and it allows using the infinite variety of genome engineering approaches developed in other models, such as strategies to facilitate transgenic bird selection, shown here. This major technological development completes the vast panel of techniques applicable to the avian model, making it one of the most versatile experimental systems available.

developmental biology↗