Dipeptidyl peptidase 4 as an injury-responsive protein in the mouse sciatic nerve

Dipeptidyl peptidase 4 (DPP4) is a membrane-bound protease known for its roles in immunity and metabolism; however, its function in the nervous system remains largely unexplored. We found that DPP4 is predominantly expressed in the Schwann cells of the sciatic nerve, and its systemic depletion in postnatal mice resulted in a decline in motor function. Importantly, the inhibition of its proteolytic activity did not affect axon regeneration, indicating that DPP4′s protease activity may not be directly involved in axon regeneration. Instead, we observed a reduction in DPP4 protein levels in the sciatic nerve after injury and increased in serum postinjury, suggesting that DPP4 may be shed into circulation, potentially mediating systemic responses following injury. These findings highlight DPP4′s importance in sensory function and its potential role in systemic responses after peripheral nerve injury.