A systems pharmacology model for inflammatory bowel disease

<div><p>Motivation</p><p>The literature on complex diseases is abundant but not always quantitative. This is particularly so for Inflammatory Bowel Disease (IBD), where many molecular pathways are qualitatively well described but this information cannot be used in traditional quantitative mathematical models employed in drug development. We propose the elaboration and validation of a logic network for IBD able to capture the information available in the literature that will facilitate the identification/validation of therapeutic targets.</p><p>Results</p><p>In this article, we propose a logic model for Inflammatory Bowel Disease (IBD) which consists of 43 nodes and 298 qualitative interactions. The model presented is able to describe the pathogenic mechanisms of the disorder and qualitatively describes the characteristic chronic inflammation. A perturbation analysis performed on the IBD network indicates that the model is robust. Also, as described in clinical trials, a simulation of anti-TNFα, anti-IL2 and Granulocyte and Monocyte Apheresis showed a decrease in the Metalloproteinases node (MMPs), which means a decrease in tissue damage. In contrast, as clinical trials have demonstrated, a simulation of anti-IL17 and anti-IFNγ or IL10 overexpression therapy did not show any major change in MMPs expression, as corresponds to a failed therapy. The model proved to be a promising <i>in silico</i> tool for the evaluation of potential therapeutic targets, the identification of new IBD biomarkers, the integration of IBD polymorphisms to anticipate responders and non-responders and can be reduced and transformed in quantitative model/s.</p></div

Old and New Lymphocyte Players in Inflammatory Bowel Disease

Polge Henri. Les toponymes en -beuf. Lettre de M. H. Polge, 6 août 1961. In: Revue Internationale d'Onomastique, 14e année N°2, juin 1962. p. 138

Transcriptional regulation of innate lymphoid cell fate.

International audienceInnate lymphoid cells (ILCs) are a recently described family of lymphoid effector cells that have important roles in immune defence, inflammation and tissue remodelling. It has been proposed that ILCs represent 'innate' homologues of differentiated effector T cells, and they have been categorized into three groups — namely, ILC1s, ILC2s and ILC3s — on the basis of their expression of cytokines and transcription factors that are typically associated with T helper 1 (T(H)1)-, T(H)2- and T(H)17-type immune responses, respectively. Indeed, remarkable similarity is seen between the specific transcription factors required for the development and diversification of different ILC groups and those that drive effector T cell differentiation. The recent identification of dedicated ILC precursors has provided a view of the mechanisms that control this first essential stage of ILC development. Here, we discuss the transcriptional mechanisms that regulate ILC development and diversification into distinct effector subsets with key roles in immunity and tissue homeostasis. We further caution against the current distinction between 'helper' versus 'killer' subsets in the evolving area of ILC nomenclature