Mitochondrial T-Cell reprogramming in virus-induced COPD exacerbation/emphysema progression (P10)

To analyze the involvement of mitochondria in the crosstalk between T cells and macrophages or BECs we hypothesize, that:

Chronic smoke exposure-induced mitochondrial dysfunction causes impaired T cell function, which enhances susceptibility to respiratory virus infections in COPD.
Recurrent virus infections excessively activate mitochondrial signaling, promote hyperinflammation and T cell exhaustion, and ultimately emphysema.
Targeting mitochondrial reprogramming of T cells and mitochondrial reactive oxygen species/mitochondrial anti-viral signaling in macrophages/BEC will allow augmentation of antiviral immune responses and prevent disease exacerbations and progression of emphysema.

We aim to investigate these hypotheses by:

Characterization of smoke-induced mitochondrial alterations affecting T cell activation, proliferation, differentiation, and contraction following infection with rhinovirus or influenza A virus in a murine model.
Determination of the role of mitochondrial pathways in virus-induced progression of emphysema.
Pharmacological and genetic interventions by using mtROS inhibitors, T cell specific knockout mice, and adoptive T cell transfer.
Translation to the human context by using biosamples for molecular biological and functional analyses (control subjects and COPD patients).
Transfer of key findings from the murine smoke-induced emphysema model to an e-cigarette mouse model.