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RNA-SEQ analysis of CD4+ T cells in presence or absence of Ikaros.

ABSTRACT: We found by microarray analysis that Ikaros is critical to limit the expression of several pro-inflammatory genes during Th17 cell polarization. To unravel the role of Ikaros in the expression of pro-inflammatory genes without Th17 polarizing cytokines, we performed an RNA-seq analysis in naive CD4+ T cells and CD4+ T cells activated with anti-CD3+anti-CD28 antibodies (Th0 condition), from WT (Ikaros f/f CD4-Cre-) and Ikaros TKO mice (Ikaros f/f CD4-Cre+).

ORGANISM(S): Mus musculus

PROVIDER: GSE157810 | GEO | 2021/04/26

REPOSITORIES: GEO

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Project description:Sanchez2017 - Inflammatory responses during acute hyperinsulinemia This model is described in the article: The CD4+ T cell regulatory network mediates inflammatory responses during acute hyperinsulinemia: a simulation study Mariana E. Martinez-Sanchez, Marcia Hiriart, Elena R. Alvarez-Buylla BMC Systems Biology Abstract: Obesity is frequently linked to insulin resistance, high insulin levels, chronic inflammation, and alterations in the behaviour of CD4+ T cells. Despite the biomedical importance of this condition, the system-level mechanisms that alter CD4+ T cell differentiation and plasticity are not well understood. We model how hyperinsulinemia alters the dynamics of the CD4+ T regulatory network, and this, in turn, modulates cell differentiation and plasticity. Different polarizing microenvironments are simulated under basal and high levels of insulin to assess impacts on cell-fate attainment and robustness in response to transient perturbations. In the presence of high levels of insulin Th1 and Th17 become more stable to transient perturbations, and their basin sizes are augmented, Tr1 cells become less stable or disappear, while TGF? producing cells remain unaltered. Hence, the model provides a dynamic system-level framework and explanation to further understand the documented and apparently paradoxical role of TGF? in both inflammation and regulation of immune responses, as well as the emergence of the adipose Treg phenotype. Furthermore, our simulations provide new predictions on the impact of the microenvironment in the coexistence of the different cell types, suggesting that in pro-Th1, pro-Th2 and pro-Th17 environments effector and regulatory cells can coexist, but that high levels of insulin severely diminish regulatory cells, especially in a pro-Th17 environment. This work provides a first step towards a system-level formal and dynamic framework to integrate further experimental data in the study of complex inflammatory diseases. This model is hosted on BioModels Database and identified by: MODEL1606020000. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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RNA-SEQ analysis of CD4+ T cells in presence or absence of Ikaros.

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