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Open AccessArticle

Generation of a Model to Predict Differentiation and Migration of Lymphocyte Subsets under Homeostatic and CNS Autoinflammatory Conditions

1
Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Albert-Schweitzer-Campus 1, Building A01, D-48149 Münster, Germany
2
Institute of Geometry and Applied Mathematics, RWTH Aachen University, Templergraben 55, D-52056 Aachen, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(6), 2046; https://doi.org/10.3390/ijms21062046
Received: 14 February 2020 / Revised: 12 March 2020 / Accepted: 13 March 2020 / Published: 17 March 2020
(This article belongs to the Special Issue CNS Drug Action in Neurodegenerative Diseases)
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. View Full-Text
Keywords: CNS inflammation; autoimmune diseases; multiple sclerosis; Susac syndrome; cerebrospinal fluid; central nervous system; flow cytometry; Markov chain model CNS inflammation; autoimmune diseases; multiple sclerosis; Susac syndrome; cerebrospinal fluid; central nervous system; flow cytometry; Markov chain model
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MDPI and ACS Style

Gross, C.C.; Pawlitzki, M.; Schulte-Mecklenbeck, A.; Rolfes, L.; Ruck, T.; Hundehege, P.; Wiendl, H.; Herty, M.; Meuth, S.G. Generation of a Model to Predict Differentiation and Migration of Lymphocyte Subsets under Homeostatic and CNS Autoinflammatory Conditions. Int. J. Mol. Sci. 2020, 21, 2046. https://doi.org/10.3390/ijms21062046

AMA Style

Gross CC, Pawlitzki M, Schulte-Mecklenbeck A, Rolfes L, Ruck T, Hundehege P, Wiendl H, Herty M, Meuth SG. Generation of a Model to Predict Differentiation and Migration of Lymphocyte Subsets under Homeostatic and CNS Autoinflammatory Conditions. International Journal of Molecular Sciences. 2020; 21(6):2046. https://doi.org/10.3390/ijms21062046

Chicago/Turabian Style

Gross, Catharina C.; Pawlitzki, Marc; Schulte-Mecklenbeck, Andreas; Rolfes, Leoni; Ruck, Tobias; Hundehege, Petra; Wiendl, Heinz; Herty, Michael; Meuth, Sven G. 2020. "Generation of a Model to Predict Differentiation and Migration of Lymphocyte Subsets under Homeostatic and CNS Autoinflammatory Conditions" Int. J. Mol. Sci. 21, no. 6: 2046. https://doi.org/10.3390/ijms21062046

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