Speaker
Description
Tertiary lymphoid structures (TLSs) are inducible ectopic lymphoid structures that emerge under chronic inflammatory conditions, including in the kidneys of patients with autoimmune diseases, and are closely associated with poor renal outcomes. Recent studies have classified TLS development into three stages correlated with chronic kidney disease severity. However, the mechanisms governing TLS initiation and stage transitions in the kidney remain unclear. To address this, we developed an interdisciplinary approach combining mathematical modeling with in vivo experimental data from a mouse model of kidney injury to capture immune cell interactions during TLS formation. The model tracks the dynamics of injured proximal tubular cells, lymphocytes, inflammatory fibroblasts, follicular dendritic cells, and other key populations. Using this framework, we found that T cell recruitment is mediated by distinct mechanisms across TLS stages: it is initiated by injury-associated signals in early stages and later sustained by components within the developing TLS structure. In addition, in silico sensitivity analysis identified stage-specific key regulators that may serve as potential therapeutic targets. Overall, our findings provide new insights into stage-dependent TLS development and offer a theoretical framework to guide future experimental and clinical studies.
