Severe infections are frequently driven by dysregulated immune responses rather than pathogen burden alone. In this project, we investigate how T cells acquire pathology-associated phenotypes during severe infections and which molecular signals govern their differentiation, activation, and pathogenic potential.

Using COVID-19 as a model, we have identified key T-cell–relevant molecular checkpoints of immunopathology, including aberrant complement activation (e.g. C3a-mediated signalling) and age-dependent rewiring of cytokine-induced STAT signalling. These pathways promote excessive T-cell activation and tissue damage and reveal aging as a critical modifier of inflammatory T-cell responses.

We extend these studies to other respiratory infections and combine spatially resolved omics with functional immune profiling to define how checkpoint signals control immune cell localization, tissue infiltration, and the balance between protective and pathological inflammation.