Biology subjects

Hamada, D.

Publications and source records attributed to Hamada, D..

3 recordsLinked to original sources

bioRxiv2026

Downregulation of Satb1 is required to prevent autoimmunity by maintaining Tfh homeostasis

T follicular helper (Tfh) cells are a specialized subset of CD4 T cells that localize to germinal centers (GC), where they provide critical help to B cells through the delivery of IL-21 and other cytokines. Here, we demonstrate that the tight control of the chromatin remodeler Special AT-rich sequence-binding protein 1 (Satb1) is key for this process, as overexpression of Satb1 drives lymphoproliferation and expansion of the T cell and B cell compartments in secondary lymphoid organs. Specifically, Satb1 overexpression induces a pronounced shift towards Tfh cell differentiation and increased GC formation accompanied by an increase in non-classed switched GC B cells and auto-antibody secretion. These findings highlight the importance of the precise regulation of Satb1 in fine-tuning CD4 T cells and B cells responses and suggest a potential role for dysregulation of Satb1 in the pathogenesis of autoimmune disease such as systemic lupus erythematodes (SLE).

immunology↗

bioRxiv2025

Molecular determinants of brain-resident CD8+ T cell formation and function

Tissue-resident memory T (Trm) cells are strategically located to provide frontline protection upon antigen re-encounter while possessing tissue-specific transcriptional programs. Whether brain Trm cells similarly adapt to their tissue environment, and to what extent their molecular signature is altered in neuropathology, remains unclear. Here we profile brain Trm cells under homeostasis and in the contexts of aging, beta-amyloidosis, and systemic viral infection. From these studies, a tissue-specific CD8+ T cell landscape emerged, defined by the expression of the transcription factor TCF-1 and the inhibitory receptor PD-1. TCF-1 was critical for the formation and phenotypic maturation of brain CD8+ Trm cells, while PD-1 signaling was necessary for robust effector function and antigen-specific recall response. In addition, the cytokine transforming growth factor (TGF)-{beta} was required for the differentiation of brain CD8+ Trm cells and restricted their transition into effector-like cells upon antigenic rechallenge. These findings highlight common as well as tissue-specific features of brain CD8+ Trm cells and provide insights into the molecular mechanisms governing their formation and function.

immunology↗

bioRxiv2024

ConvexGating infers gating strategies from clusters in single cell cytometry data

Manual expert gating remains common practice for the definition of specific cell populations in the analysis of flow cytometry data. The increasing number of measured parameters per individual cell and high inter-rater variability makes manual gating inconsistent in many scenarios such as multi-center studies. Here, we propose ConvexGating, an AI tool that automatically learns gating strategies in an unbiased, fully data-driven, yet interpretable manner. ConvexGating scales efficiently with increasing parameter space, creating proficient strategies with low-contamination in the extracted population for previously known and so far unknown or ill-defined cell populations. The inferred strategies are independent of parent populations, for instance, plasmacytoid dendritic cells (pDCs) can be fully identified as CD45RA- CD123+. In addition to flow cytometry data, ConvexGating derives gating strategies for cyTOF (Cytometry by Time of Flight) and CITEseq (Cellular Indexing of Transcriptomes and Epitopes by Sequencing) data and supports optimal design of marker panels for cell sorting.

immunology↗