1. Generation of a Model to Predict Differentiation and Migration of Lymphocyte Subsets under Homeostatic and CNS Autoinflammatory Conditions.
- Author
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Gross CC, Pawlitzki M, Schulte-Mecklenbeck A, Rolfes L, Ruck T, Hundehege P, Wiendl H, Herty M, and Meuth SG
- Subjects
- Adolescent, Adult, Autoimmune Diseases metabolism, Biomarkers, Central Nervous System metabolism, Central Nervous System Diseases metabolism, Central Nervous System Diseases pathology, Child, Disease Susceptibility immunology, Female, Humans, Immunophenotyping, Inflammation metabolism, Inflammation pathology, Lymphocyte Count, Lymphocyte Subsets metabolism, Male, Middle Aged, Young Adult, Autoimmune Diseases etiology, Cell Movement immunology, Central Nervous System immunology, Central Nervous System Diseases etiology, Homeostasis, Inflammation etiology, Lymphocyte Subsets immunology, Models, Biological
- Abstract
The central nervous system (CNS) is an immune-privileged compartment that is separated from the circulating blood and the peripheral organs by the blood-brain and the blood-cerebrospinal fluid (CSF) barriers. Transmigration of lymphocyte subsets across these barriers and their activation/differentiation within the periphery and intrathecal compartments in health and autoinflammatory CNS disease are complex. Mathematical models are warranted that qualitatively and quantitatively predict the distribution and differentiation stages of lymphocyte subsets in the blood and CSF. Here, we propose a probabilistic mathematical model that (i) correctly reproduces acquired data on location and differentiation states of distinct lymphocyte subsets under homeostatic and neuroinflammatory conditions, (ii) provides a quantitative assessment of differentiation and transmigration rates under these conditions, (iii) correctly predicts the qualitative behavior of immune-modulating therapies, (iv) and enables simulation-based prediction of distribution and differentiation stages of lymphocyte subsets in the case of limited access to biomaterial. Taken together, this model might reduce future measurements in the CSF compartment and allows for the assessment of the effectiveness of different immune-modulating therapies.
- Published
- 2020
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