Model-driven Experimentation: A new approach to understand mechanisms of tertiary lymphoid tissue formation, function and therapeutic resolution.
- 1Biology, University of York, United Kingdom
- 2Electronics, University of York, United Kingdom
The molecular and cellular processes driving the formation of secondary lymphoid tissues have been extensively studied using a combination of mouse knockouts, lineage specific reporter mice, gene expression analysis, immunohistochemistry and flow cytometry. However, the mechanisms driving the formation and function of tertiary lymphoid tissue (TLT) experimental techniques have proven to be more enigmatic and controversial due to differences between experimental models and human disease pathology. Systems-based approaches including data-driven biological network analysis (Gene Interaction Network, Metabolic Pathway Network, Cell-Cell signalling & cascade networks) and mechanistic modelling afford a novel perspective from which to understand TLT formation and identify mechanisms that may lead to the resolution of tissue pathology. In this perspective, we make the case for applying model-driven experimentation using two case studies which combined simulations with experiments to identify mechanisms driving lymphoid tissue formation and function, and then discuss potential applications of this experimental paradigm to identify novel therapeutic targets for TLT pathology.
Keywords: Multi-scsale modelling, tertiary lymphoid tissue, Systems Immunology, Stromal Cells, innate lymphoid cells
Citation: Butler JA, Cosgrove J, Alden K, Timmis J and Coles MC
Received: 26 Aug 2016;
Accepted: 16 Dec 2016.
Edited by:Andreas Habenicht, Ludwig-Maximilians-Universität München, Germany
Reviewed by:Jorge Caamano, University of Birmingham, United Kingdom
Neil Macritchie, University of Glasgow, Scotland
Copyright: © 2016 Butler, Cosgrove, Alden, Timmis and Coles. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Prof. Mark C. Coles, University of York, Biology, Wentworth Way, York, YO10 5DD, United Kingdom, firstname.lastname@example.org