Figure 7.

Schematic representation of GDAP1L1-modulated macrophage trafficking and inflammation cytokine responses to regulate psoriatic skin inflammation. The activation of antigen-presenting cells, such as macrophages, initiated the development of psoriatic inflammation. The ligand of TLR 7/8, IMQ, activated cytokine and chemokine production in macrophages through MAPK and NK-κB phosphorylation, which was in the GDAP1L1-dependent manner. Activated macrophages could traffic to the skin-draining lymph node and the dermis via vessel and contribute to T cell-mediated and epidermis-mediated psoriasiform skin inflammation. In turn, the cytokines and chemokines from activated macrophages rescued neutrophils, which caused epidermal proliferation. We found that IMQ induced GDAP1L1-dependent Drp1 S616 phosphorylation and then caused mitochondria translocation of GDAP1L1 and phosphorylated Drp1 S616, leading to mitochondrial fission, which played an important role in macrophage trafficking and inflammatory cytokine production.