New tool predicts if immunotherapy will mistakenly attack healthycells frontiersin
DA conceived the original idea behind this work. DA and AF designed the methods and experiments. AF selected the datasets, implemented the methods, and executed the experiments. DA and AF analyzed and interpreted the results. AF wrote the first draft of the manuscript. All authors contributed to the article and approved the submitted version.AF and DA were supported in part by funds from the University of Houston.
Two-dimensional plot displaying amino acid distribution according to the first and second principal components from the dimensionality reduction. Similar residues are grouped at closest distances, e.g., Isoleucine, Valine, and Leucine. Proline and Arginine are outliers.Histograms of Coulomb interactions. Short-range Coulomb interactions were calculated using the software gmx energy from Gromacs, and divided into intervals .
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Prominent epigenetic and transcriptomic changes in CD4+ and CD8+ T cells during and after pregnancy in women with multiple sclerosis and controls - Journal of NeuroinflammationBackground Multiple sclerosis (MS) is a neuroinflammatory disease in which pregnancy leads to a temporary amelioration in disease activity as indicated by the profound decrease in relapses rate during the 3rd trimester of pregnancy. CD4+ and CD8+ T cells are implicated in MS pathogenesis as being key regulators of inflammation and brain lesion formation. Although Tcells are prime candidates for the pregnancy-associated improvement of MS, the precise mechanisms are yet unclear, and in particular, a deep characterization of the epigenetic and transcriptomic events that occur in peripheral T cells during pregnancy in MS is lacking. Methods Women with MS and healthy controls were longitudinally sampled before, during (1st, 2nd and 3rd trimesters) and after pregnancy. DNA methylation array and RNA sequencing were performed on paired CD4+ and CD8+ T cells samples. Differential analysis and network-based approaches were used to analyze the global dynamics of epigenetic and transcriptomic changes. Results Both DNA methylation and RNA sequencing revealed a prominent regulation, mostly peaking in the 3rd trimester and reversing post-partum, thus mirroring the clinical course with improvement followed by a worsening in disease activity. This rebound pattern was found to represent a general adaptation of the maternal immune system, with only minor differences between MS and controls. By using a network-based approach, we highlighted several genes at the core of this pregnancy-induced regulation, which were found to be enriched for genes and pathways previously reported to be involved in MS. Moreover, these pathways were enriched for in vitro stimulated genes and pregnancy hormones targets. Conclusion This study represents, to our knowledge, the first in-depth investigation of the methylation and expression changes in peripheral CD4+ and CD8+ T cells during pregnancy in MS. Our findings indicate that pregnancy induces profound changes in peripheral T cells, in both MS and health
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