Tacrolimus reverses the pemphigus vulgaris serum-enhanced expression of desmoglein in HaCaT cells

Abstract Background: Pemphigus vulgaris (PV) is associated with autoantibodies against desmoglein (Dsg), including Dsg1 and Dsg3. However, the precise mechanism by which acantholysis occurs in response to PV-IgG and the effect of tacrolimus on PV remains unclear. Method: Human HaCaT keratinocytes were co-cultured with DMEM medium containing 5% PV-sera to establish a cell model of pemphigus in order to determine the effect of PV-sera and tacrolimus on Dsg mRNA transcription and protein expression in HaCaT cells. Dsg protein expression in HaCaT cells was evaluated by Western blotting and Dsg mRNA transcription by real-time PCR (RT-PCR ). The distribution of Dsg1 and Dsg3 in HaCaT cells was determined by indirect immunofluorescence (IIF). Results: The application of 5% PV serum resulted in an increase in Dsg1 and Dsg3 transcription and expression levels, whereas tacrolimus suppressed Dsg1 and Dsg3 expression. Tacrolimus inhibited PV serum-induced disruption of cell-cell contacts. Tacrolimus also down-regulated Dsg1 and Dsg3 expression compared with PV. IIF revealed that Dsg1 linear deposits on the surface of HaCaT cells in the PV-sera group disappeared and were replaced by granular and agglomerated fluorescent particles on the cell surface, whereas the Dsg3 linear deposits were still present, however this effect could be reversed by tacrolimus. Conclusion: The Dsg3 antibody disrupts desmosome junctions by inducing endocytosis, resulting in desmosomal dissociation. Tacrolimus can reverse PV serum-induced enhancement Dsg expression in HaCaT cells.