The skin is a complex organ that contains a plethora of cell types and annexed structures, including hair follicles. Altogether they conduct essential functions, such as temperature control, tissue sensing, barrier maintenance and immune defense. Our study is focused on the role of immunometabolism in age-associated skin processes and how controlling T cell metabolism can contribute to regulate skin homeostasis, hair growth and tissue regeneration.
To address this aim, we have used a mouse model lacking the mitochondrial transcription factor A (Tfam) in CD4-expressing cells (Tfamfl/fl CD4Cre mice). Since Tfam is essential for mitochondrial DNA stabilization and replication, its absence leads to a severe mitochondrial dysfunction. Thus, T lymphocytes shift their metabolism from oxidative phosphorylation towards glycolysis, becoming proinflammatory. We are interested in investigating how stem cell dynamics and tissue homeostasis are indirectly affected by these immunometabolic alterations.
We first analysed the bulge stem cell compartment of hair follicles. Both pulse and long-chase experiments based on bromodeoxyuridine incorporation and retention by quiescent cells and flow cytometry assays to identify the CD49fhi CD34+ cell pool suggested altered stem cell mobilisation in Tfamfl/fl CD4Cre mice. On a step forward, functional experiments challenging skin homeostasis evidenced a striking delay in wound healing in response to 2nd degree burns in Tfam deficient animals compared to controls, which was accompanied by a delay in hair regrowth. Overall, our results point to deficient hair follicle stem cell function ultimately caused by altered T cell metabolism, that in turn promotes age-associated skin signs.

Immunometabolic imbalance fosters skin ageing