Targeting Dipeptidyl-peptidase-4 (DPP4) in systemic sclerosis and related fibrotic diseases

• Applicant: Dr. Alina Ramming
• Subject Area: Rheumatology
• Term: since 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 422621469

Fibrotic diseases can be considered as a consequence of persistent, exaggerated and uncontrolled tissue repair processes. Systemic sclerosis (SSc) is associated with a high mortality and effective anti-fibrotic therapies are still lacking. Dipeptidyl-peptidase-4 (DPP4) has been recently shown to identify a distinct dermal lineage of fibroblasts involved in scar formation.We have demonstrated that DPP4-positive cells are increased not only in experimental fibrosis, but also in skin biopsies from SSc patients as compared to healthy volunteers. DPP4-inhibition showed potent anti-fibrotic effects in bleomycin-induced skin fibrosis. However, the specific role of DPP4-positive fibroblasts in fibrotic diseases is unknown. We aim in this study to characterize the phenotype of DPP4-positive fibroblasts and assess the potential pro-fibrotic properties of DPP4-positive fibroblasts. Further we plan to test DPP4-inhibitors in mouse models of fibrotic diseases resembling, different subtypes and stages of other fibrotic diseases such as chronic graft-versus-host disease mouse model, topoisomerase mouse model and models of pulmonary fibrosis. These results may have direct clinical implications as DPP4-inhibitors are already in clinical use for diabetes.

• DFG Programme: Research Grants