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Simulating CXCR5 Dynamics in Complex Tissue Microenvironments.

Jason Cosgrove1,2, Kieran Alden1, Jens V Stein3

  • 1Department of Electronic Engineering, University of York, York, United Kingdom.

Frontiers in Immunology
|September 24, 2021
PubMed
Summary
This summary is machine-generated.

Immune cells use chemokine receptors to navigate tissues. This study shows receptor signaling dynamics, not just numbers, are key for efficient cell migration and antigen scanning in complex environments.

Keywords:
B cellsG-protein coupled receptorschemokinesmathematical modellingsystems biology

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Area of Science:

  • Immunology
  • Computational Biology
  • Cell Biology

Background:

  • Immune cells navigate complex tissue microenvironments by sensing molecular gradients.
  • G-protein coupled receptors (GPCRs) are crucial for this sensing mechanism.
  • Chemokine receptor activity in situ is poorly understood due to receptor complexity and multimodal gradients.

Purpose of the Study:

  • To investigate the spatiotemporal dynamics of CXCR5 expression in a simulated B-follicle.
  • To understand how chemokine receptor activity influences immune cell migration and antigen scanning.
  • To determine the relative importance of receptor numbers versus signaling dynamics in cellular navigation.

Main Methods:

  • Application of a modeling and simulation approach.
  • Analysis of spatiotemporal dynamics of CXCR5 expression at single-cell resolution within an in silico B-follicle.
  • Multi-objective optimization analysis to identify key regulatory factors.

Main Results:

  • In silico B-cell scanning is robust to variations in receptor numbers and individual kinetic rates.
  • Scanning efficiency is sensitive to simultaneous alterations in multiple parameters.
  • Rapid modulation of CXCR5 activity (binding, desensitization, recycling) is essential for optimal antigen scanning.

Conclusions:

  • Chemokine receptor signaling dynamics play a more significant role in regulating migration within complex tissue microenvironments than total receptor numbers.
  • This study provides insights into the mechanisms governing immune cell navigation and positioning.