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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:

  1. 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.
  2. Determination of the role of mitochondrial pathways in virus-induced progression of emphysema.
  3. Pharmacological and genetic interventions by using mtROS inhibitors, T cell specific knockout mice, and adoptive T cell transfer.
  4. Translation to the human context by using biosamples for molecular biological and functional analyses (control subjects and COPD patients).
  5. Transfer of key findings from the murine smoke-induced emphysema model to an e-cigarette mouse model.

Detail of this project can be found here.