Simulating CXCR5 Dynamics in Complex Tissue Microenvironments

To effectively navigate complex tissue microenvironments, immune cells sense molecular concentration gradients using G-protein coupled receptors. However, due to the complexity of receptor activity, and the multimodal nature of chemokine gradients in vivo , chemokine receptor activity in situ is poo...

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Vydáno v:Frontiers in immunology Ročník 12; s. 703088
Hlavní autoři: Cosgrove, Jason, Alden, Kieran, Stein, Jens V., Coles, Mark C., Timmis, Jon
Médium: Journal Article
Jazyk:angličtina
Vydáno: Switzerland Frontiers 07.09.2021
Frontiers Media S.A
Témata:
B cells
B-Lymphocytes - immunology
Biochemistry, Molecular Biology
Cellular Microenvironment - immunology
chemokines
G-protein coupled receptors
Genomics
Humans
Immunology
Innate immunity
Life Sciences
mathematical modelling
Models, Immunological
Organ Specificity - immunology
Receptors, Chemokine - immunology
Receptors, CXCR5 - immunology
Signal Transduction - immunology
systems biology
systems biology
mathematical modelling
B cells
G-protein coupled receptors
chemokines
ISSN:1664-3224, 1664-3224
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Shrnutí:To effectively navigate complex tissue microenvironments, immune cells sense molecular concentration gradients using G-protein coupled receptors. However, due to the complexity of receptor activity, and the multimodal nature of chemokine gradients in vivo , chemokine receptor activity in situ is poorly understood. To address this issue, we apply a modelling and simulation approach that permits analysis of the spatiotemporal dynamics of CXCR5 expression within an in silico B-follicle with single-cell resolution. Using this approach, we show that that in silico B-cell scanning is robust to changes in receptor numbers and changes in individual kinetic rates of receptor activity, but sensitive to global perturbations where multiple parameters are altered simultaneously. Through multi-objective optimization analysis we find that the rapid modulation of CXCR5 activity through receptor binding, desensitization and recycling is required for optimal antigen scanning rates. From these analyses we predict that chemokine receptor signaling dynamics regulate migration in complex tissue microenvironments to a greater extent than the total numbers of receptors on the cell surface.
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This article was submitted to Systems Immunology, a section of the journal Frontiers in Immunology
Edited by: Peter Sims, Columbia University, United States
Reviewed by: Jamie Berta Spangler, Johns Hopkins University, United States; Irina Kufareva, University of California, San Diego, United States
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2021.703088