Perspectives on Systems Modeling of Human Peripheral Blood Mononuclear Cells

Abstract

Human peripheral blood mononuclear cells (PBMCs) are the key drivers of the immune responses. These cells undergo activation, proliferation and differentiation into various subsets. During these processes they initiate metabolic reprogramming, which is coordinated by specific gene and protein activities. PBMCs as a model system have been widely used to study metabolic and autoimmune diseases. Herein we review various omics and systems-based approaches such as transcriptomics, epigenomics, proteomics, and metabolomics as applied to PBMCs, particularly T helper subsets, that unveiled disease markers and the underlying mechanisms. We also discuss and emphasize several aspects of T cell metabolic modeling in healthy and disease states using genome-scale metabolic models.

Comprehensive Profiling of the Circulatory miRNAome Response to a High Protein Diet in Elderly Men: A Potential Role in Inflammatory Response Modulation

“…Alterations in these pathways have been previously described as associated with inflammation and related pathways . Additional genes downstream of the five regulated miRNAs were identified using literature search as being targeted by ≥3 of the differentially expressed miRNAs, in at least two models among animals, humans, or cell lines, as well as being shown to play a role in PBMC function . Evidence for the inclusion of the additional genes ( TNF‐α, IL‐6, IL6R, IL‐8, pTEN, mTOR, VEGF , and IGF1R) is shown in Table S7, Supporting Information.…”

Metabolic Alterations in Human Peripheral Blood Mononuclear Cells Associate with Progression to Islet Autoimmunity and Type 1 Diabetes

“…In order to understand the regulation of metabolic pathways in PBMCs after seroconversion and T1D progression, genome-scale metabolic models (GEMs) (Bordbar et al, 2012;Sen et al, 2018) of PBMCs were developed. Gene expression or transcriptomics datasets were used to contextualize these models for the P1Ab, P1TD and CTRL groups.…”

“…The datasets from these studies were downloaded from ArrayExpress (www.ebi.ac.uk; accession number E-MTAB-1724). Expression data from 15 non-progressors (P1Ab), 51 cases of T1D (PT1D), and their controls (CTRL) were selected for genome-scale metabolic modeling (GSMM) (Bordbar et al, 2012;Orth et al, 2010;Sen et al, 2017). In addition, differential expression of genes (DEG) for P1Ab Vs. CTRL, PT1D Vs. CTRL and PT1D Vs. P1Ab groups was performed.…”

“…In fact, external perturbation of key metabolic processes such as glycolysis and amino acid metabolism have already been shown to impair T-cell activation, differentiation and cytokine production (Almeida et al, 2016;Berod et al, 2014;Geiger et al, 2016;Ma et al, 2017). Human peripheral blood mononuclear cells (PBMCs), including T cells (~70%), B cells (~15%), monocytes (~5 %), dendritic cells (~1%) and natural killer (NK) cells (~10%) obtained from healthy donors and T1D progressors are already being investigated in order to better understand this phenomenon (Sen et al 2018). Such efforts seek to elucidate how immune cell metabolic processes are altered in seroconversion and progression to overt T1D; currently a largely unknown area.…”

PBMC Treatment Significantly Changes Gene Expression Regulation in Horses

“…Peripheral blood mononuclear cells (PBMCs) are cells with a single round nucleus (T-cells, B-cells, and natural killer (NK) cells, etc.) that are readily isolated from whole blood [1]. The transcriptional responses of PBMCs in four different in vitro contexts has been measured with RNAseq data in horses: no treatment (MCK) to represent baseline RNA expression, lipopolysaccharides (LPS) to mimic an inflammatory response, recombinant cyathostomin antigen (RCA) to mimic response to parasitic antigens, and hay-dust extract (HDE) to mimic severe equine asthma (SEA) (formerly known as recurrent airway obstruction, RAO) exacerbation in susceptible horses [2–5].…”