Jun 28, 2017

The CD4+ T cell regulatory network mediates inflammatory responses during acute hyperinsulinemia: a simulation study

BMC Systems Biology
Mariana Esther Martinez-SanchezElena R Alvarez-Buylla


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 TGFβ 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 TGFβ 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 o...Continue Reading

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Mentioned in this Paper

Compensatory Hyperinsulinemia
Immune Response
Transforming Growth Factor beta
Systemic Inflammatory Response Syndrome
TGFA protein, human
Regulation of Biological Process

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