Speaker
Description
Immune responses are tightly regulated by a diverse set of interacting immune-cell populations, and immune-cell communication pathways are routinely targeted by immunotherapy in autoimmune diseases and cancer. However, a quantitative understanding of immune-cell regulation in vivo is only beginning to emerge \cite{1}. We assessed cytokine reaction-diffusion dynamics using a 4D finite-element based modeling framework \cite{2}. We found that spatial cytokine gradients robustly arise in physiological parameter regimes and are critical for effective paracrine signaling, and they do not arise by diffusion and uptake alone, but rather depend on properties of the cell population such as an all-or-none behavior of cytokine secreting cells. Next, we explored the effect of cytokine gradients in the context of motile cell populations in the lymph node and the tumor microenvironment, employing both cellular Potts models and a numerically efficient formulation of cytokine gradients based on a homogenization approach. Further, we developed a general mathematical framework for analysis of interactive immune-cell population dynamics, accounting for cell-cell interactions, cell-proliferation, and cell-differentiation by means of measurable response-time distributions \cite{3}. We employed that framework to describe the onset of lupus nephritis, the renal manifestation of systemic lupus erythematosus (SLE) \cite{4}. Starting from analysis of single-cell RNA-sequencing data on innate lymphoid cells, our mathematical model reconciles that experimental data with long-standing clinical observations such as elevated autoantibodies and interferons in individuals with genetic predisposition for SLE. Overall, our results from model simulations and data analysis highlight the complex dynamics imposed by cell-cell signaling networks in the immune system, with implications for therapeutic intervention.
Bibliography
@ARTICLE{1,
title = "Untangling cell--cell communication networks and on-treatment
response in immunotherapy",
author = "Steinheuer, Lisa Maria and Kl{\"u}mper, Niklas and Bald, Tobias
and Thurley, Kevin",
journal = "Curr. Opin. Syst. Biol.",
publisher = "Elsevier BV",
volume = 40,
number = 100534,
pages = "100534",
month = mar,
year = 2025,
}
@ARTICLE{2,
title = "Diffusion-limited cytokine signaling in {T} cell populations",
author = "Brunner, Patrick and Kiwitz, Lukas and Li, Lisa and Thurley,
Kevin",
journal = "iScience",
publisher = "Elsevier BV",
volume = 27,
number = 6,
pages = "110134",
month = jun,
year = 2024,
}
@ARTICLE{3,
title = "Distribution modeling quantifies collective {TH} cell decision
circuits in chronic inflammation",
author = "Burt, Philipp and Thurley, Kevin",
journal = "Sci. Adv.",
publisher = "American Association for the Advancement of Science (AAAS)",
volume = 9,
number = 37,
pages = "eadg7668",
month = sep,
year = 2023,
}
@ARTICLE{4,
title = "Amplification cycles through innate lymphoid cells at the onset
of lupus nephritis",
author = "Kreider, Rosa L and Biniaris-Georgallis, Stylianos-Iason and
Grothey, Bastian and Triantafyllopoulou, Antigoni and
Steinheuer, Lisa M and Thurley, Kevin",
journal = "Front. Immunol.",
publisher = "Frontiers Media SA",
volume = 17,
number = 1756560,
pages = "1756560",
month = mar,
year = 2026,
language = "en"
}
