Biology subjects

Soto-Ugaldi, L. F.

Publications and source records attributed to Soto-Ugaldi, L. F..

5 recordsLinked to original sources

bioRxiv2026

Systemic Autoimmunity Remodels Microbiota-Reactive CD4⁺ T Cell Immunity

The gut microbiota contributes to autoimmune disease, yet how systemic autoimmunity reshapes microbiota-reactive CD4 T cell responses and how these cells influence disease progression remain poorly understood. Previous studies have linked microbiota-reactive T cells and lupus-associated pathobionts to disease pathogenesis, but the pathways that regulate the accumulation, differentiation, and pathogenicity of microbiota-reactive T cells during autoimmunity remain unclear. Here, we show that systemic autoimmunity drives the expansion, accumulation, and functional differentiation of microbiota-reactive CD4 T cells. Using segmented filamentous bacteria tetramers, we identify antigen-defined microbiota-reactive CD4 T cells that undergo systemic accumulation and Th1/Tfh polarization during disease. We further identify reactivation of intestinal dendritic cell trafficking as a mechanism linking systemic autoimmunity to the accumulation of microbiota-reactive CD4 T cells in peripheral tissues. In contrast to commensal-reactive T cells, CD4 T cells conditioned by the lupus-associated pathobiont Enterococcus gallinarum markedly exacerbate autoimmunity following adoptive transfer through IL-21- and IFN{gamma}-dependent mechanisms. Together, these findings demonstrate that systemic autoimmunity reshapes microbiota-reactive CD4 T cell immunity and establish microbial context as a critical determinant of microbiota-reactive CD4 T cell pathogenicity.

immunology↗

bioRxiv2026

fastCDS: proteome-scale mapping of protein domains to genomic coordinates

SummaryMapping protein regions to genomic coordinates underpins the study of exon architecture and the interpretation of clinical variants in their exon context. Existing tools resolve individual queries accurately but scale poorly to proteome-wide analyses. We present fastCDS, a C++ toolkit with command line and Python interfaces for rapid protein-to-genome coordinate mapping from GTF annotations. It matches the accuracy of existing methods while running at least two to three orders of magnitude faster. Mapping all human Pfam domains in seconds, we used the resulting atlas to examine how exonic architecture varies with domain function. Availability and ImplementationfastCDS is freely available under the MIT license at {{https://github.com/SotoLF/fastCDS}} and can be installed with pip install fastCDS or mamba install -c bioconda fastCDS. Pre-built GTF genome indices are archived at Zenodo, DOI: https://zenodo.org/records/21436146. Contactlsoto@rockefeller.edu Supplementary InformationSupplementary data are available at Bioinformatics online.

bioinformatics↗

bioRxiv2026

A commensally regulated immune rheostat fine-tunes skin barrier fitness

At the skins surface, the epidermis must balance stem cell renewal with barrier maintenance to withstand environmental stress and shield against pathogens. Here, we identify a microbial-immune-epithelial feedback mechanism that integrates environmental information into stem cell regulation. Specifically, we show that Langerhans cells--an intra-epithelial macrophage population-- orchestrate this circuit by producing prostaglandin E2, which restrains stem cell proliferation, promotes epidermal differentiation and maintains barrier integrity during homeostasis. Upon pathway disruption, stem cells become overactivated, impairing differentiation and compromising barrier function. Upstream, Langerhans cell activity is tuned by the local microbial environment in a rheostat-like fashion, coupling commensal sensing to stem cell control. Our findings provide a general framework for how barrier tissues achieve adaptive homeostasis amid continual external challenge.

immunology↗

bioRxiv2025

Viral transcriptional regulators extensively rewire host pathways through diverse mechanisms

Viral transcriptional regulators (vTRs) reprogram host gene regulatory networks to promote replication, persistence, and immune evasion. Despite the identification of hundreds of vTRs in human viruses, how they rewire host pathways remains unclear. Here, we systematically profiled 95 vTRs from diverse human viruses across multiple functional assays. vTRs perturb immune, cell proliferation/death, and signaling pathways through various mechanisms; some bind DNA directly, others cooperate or antagonize human transcription factors (hTFs), and some remodel chromatin. vTRs can act as activators or repressors and recruit similar but not identical repertoires of proteins as hTFs. These findings reveal vTRs as versatile transcriptional modulators that converge on conserved host "pressure points" while diversifying across pathways to promote viral replication and persistence. Notably, many vTR dysregulate genes within autoimmune, neurological, and cardiovascular risk loci, revealing mechanistic links to disease. Together, we provide a comprehensive resource for understanding and targeting viral control of human transcription.

genomics↗

bioRxiv2024

A large-scale cancer-specific protein-DNA interaction network

Cancer development and progression are generally associated with dysregulation of gene expression, often resulting from changes in transcription factor (TF) sequence or expression. Identifying key TFs involved in cancer gene regulation provides a framework for potential new therapeutics. This study presents a large-scale cancer gene TF-DNA interaction network as well as an extensive promoter clone resource for future studies. Most highly connected TFs do not show a preference for binding to promoters of genes associated with either good or poor cancer prognosis, suggesting that emerging strategies aimed at shifting gene expression balance between these two prognostic groups may be inherently complex. However, we identified potential for oncogene targeted therapeutics, with half of the tested oncogenes being potentially repressed by influencing specific activator or bifunctional TFs. Finally, we investigate the role of intrinsically disordered regions within the key cancer-related TF estrogen receptor [a] (ESR1) on DNA binding and transcriptional activity, and found that these regions can have complex trade-offs in TF function. Altogether, our study not only broadens our knowledge of TFs involved in the cancer gene regulatory network but also provides a valuable resource for future studies, laying a foundation for potential therapeutic strategies targeting TFs in cancer.

systems biology↗