TY - JOUR
T1 - Model-driven Experimentation: A new approach to understand mechanisms of tertiary lymphoid tissue formation, function and therapeutic resolution.
AU - Butler, James Andrew
AU - Cosgrove, Jason
AU - Alden, Kieran James
AU - Timmis, Jonathan Ian
AU - Coles, Mark Christopher
N1 - © 2016 Butler, Cosgrove, Alden, Timmis and Coles.
PY - 2016/12/16
Y1 - 2016/12/16
N2 - 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.
AB - 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.
U2 - 10.3389/fimmu.2016.00658
DO - 10.3389/fimmu.2016.00658
M3 - Article
SN - 1664-3224
SP - 1
EP - 23
JO - Frontiers in immunology
JF - Frontiers in immunology
ER -