TcellSubC: An Atlas of the Subcellular Proteome of Human T Cells.

We have curated an in-depth subcellular proteomic map of primary human CD4+ T cells, divided into cytosolic, nuclear and membrane fractions generated by an optimized fractionation and HiRIEF-LC-MS/MS workflow for limited amounts of primary cells. The subcellular proteome of T cells was mapped under steady state conditions, as well as upon 15 min and 1 h of T cell receptor (TCR) stimulation, respectively. We quantified the subcellular distribution of 6,572 proteins and identified a subset of 237 potentially translocating proteins, including both well-known examples and novel ones.

Challenges in the Multivariate Analysis of Mass Cytometry Data: The Effect of Randomization.

Cytometry by time-of-flight (CyTOF) has emerged as a high-throughput single cell technology able to provide large samples of protein readouts. Already, there exists a large pool of advanced high-dimensional analysis algorithms that explore the observed heterogeneous distributions making intriguing biological inferences. A fact largely overlooked by these methods, however, is the effect of the established data preprocessing pipeline to the distributions of the measured quantities.

Phosphatase inhibitor PPP1R11 modulates resistance of human T cells toward Treg-mediated suppression of cytokine expression.

Regulatory T cells (Tregs) act as indispensable unit for maintaining peripheral immune tolerance mainly by regulating effector T cells. T cells resistant to suppression by Tregs pose therapeutic challenges in the treatment of autoimmune diseases, while augmenting susceptibility to suppression may be desirable for cancer therapy. To understand the cell intrinsic signals in T cells during suppression by Tregs, we have previously performed a global phosphoproteomic characterization.

Time-resolved transcriptome and proteome landscape of human regulatory T cell (Treg) differentiation reveals novel regulators of FOXP3.

Background: Regulatory T cells (Tregs) expressing the transcription factor FOXP3 are crucial mediators of self-tolerance, preventing autoimmune diseases but possibly hampering tumor rejection. Clinical manipulation of Tregs is of great interest, and first-in-man trials of Treg transfer have achieved promising outcomes. Yet, the mechanisms governing induced Treg (iTreg) differentiation and the regulation of FOXP3 are incompletely understood.

SCENERY: a web application for (causal) network reconstruction from cytometry data.

Flow and mass cytometry technologies can probe proteins as biological markers in thousands of individual cells simultaneously, providing unprecedented opportunities for reconstructing networks of protein interactions through machine learning algorithms. The network reconstruction (NR) problem has been well-studied by the machine learning community. However, the potentials of available methods remain largely unknown to the cytometry community, mainly due to their intrinsic complexity and the lack of comprehensive, powerful and easy-to-use NR software implementations specific for cytometry data.

TGF-β Affects the Differentiation of Human GM-CSF CD4 T Cells in an Activation- and Sodium-Dependent Manner.

The cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) is involved in the pathogenesis of chronic inflammatory diseases such as multiple sclerosis. However, the environmental cues promoting differentiation of GM-CSF producing T cells are unclear. Herein, we performed a broad experimental screening of cytokines and data-driven analysis assessing their ability to induce human GM-CSF CD4 T cells and their subpopulations.