Integrative Computational Modeling of the Lymph Node Stromal Cell Landscape.

Mario Novkovic,Hung-Wei Cheng,Lucas Onder,Burkhard Ludewig,Gennady Bocharov

doi:10.3389/fimmu.2018.02428

Abstract

Adaptive immune responses develop in secondary lymphoid organs such as lymph nodes (LNs) in a well-coordinated series of interactions between migrating immune cells and resident stromal cells. Although many processes that occur in LNs are well understood from an immunological point of view, our understanding of the fundamental organization and mechanisms that drive these processes is still incomplete. The aim of systems biology approaches is to unravel the complexity of biological systems and describe emergent properties that arise from interactions between individual constituents of the system. The immune system is greater than the sum of its parts, as is the case with any sufficiently complex system. Here, we review recent work and developments of computational LN models with focus on the structure and organization of the stromal cells. We explore various mathematical studies of intranodal T cell motility and migration, their interactions with the LN-resident stromal cells, and computational models of functional chemokine gradient fields and lymph flow dynamics. Lastly, we discuss briefly the importance of hybrid and multi-scale modeling approaches in immunology and the technical challenges involved.

Highlights

The lymphatic vascular system extends throughout the body, collecting interstitial tissue fluid through a network of initial lymphatic vessels [1]
Lévy walks and subdiffusive random motion [49, 60]. It has been shown in a recent report using Agent-Based Models (ABM) that naive T cells in lymph nodes (LNs) exhibit a type of superdiffusive walk which fits best as a lognormal modulated correlated random walk among the idealized computational models studied [61] (Table 1)
Quantitative and computational in silico models in immunology have become critical for understanding the emergent properties of both single cells and whole tissues [110, 111]

Summary

Introduction

The lymphatic vascular system extends throughout the body, collecting interstitial tissue fluid through a network of initial lymphatic vessels [1]. FRCs in the T cell zone (TRC) produce homeostatic chemokines CCL19 and CCL21, guiding T cells and DCs into the relevant compartments and facilitating T-DC interactions necessary for developing adaptive immunity and antiviral responses [31,32,33] (Figure 1A). It has been shown in a recent report using Agent-Based Models (ABM) that naive T cells in LNs exhibit a type of superdiffusive walk which fits best as a lognormal modulated correlated random walk among the idealized computational models studied [61] (Table 1).

Results

Conclusion