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2016 ; 7
(ä): 658
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English Wikipedia
Model-Driven Experimentation: A New Approach to Understand Mechanisms of Tertiary
Lymphoid Tissue Formation, Function, and Therapeutic Resolution
#MMPMID28421068
Butler JA
; Cosgrove J
; Alden K
; Timmis J
; Coles MC
Front Immunol
2016[]; 7
(ä): 658
PMID28421068
show ga
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 signaling, and cascade networks) and mechanistic modeling 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.