Figure 6. Putative model of primary event leading to loss of melanocytes in depigmenting disorders.

Type 1 cytokines TNF-α and IFN-γ produced by activated Trm cells induce an E-cadherin defect in melanocytes. TNF-α and IFN-γ induce the production of MMP-9 by epidermal cells, especially keratinocytes, that cleave E-cadherin (Ecad) to release its soluble form. E-cadherin cleavage leads to melanocyte destabilization. This effect is inhibited in the presence of MMP-9 or JAK inhibitors.