Superficial Dsg2 Expression Limits Epidermal Blister Formation Mediated by Pemphigus Foliaceus Antibodies and Exfoliative Toxins
Figure 5
Superficial expression of Dsg2 reduces disruption of Dsg1 in response to PF Ig. Newborn WT and Dsg2 Tg mice were injected subcutaneously with PF Ig, and, 18 hours later, back skin samples were frozen in OCT or were fixed in formalin and embedded in paraffin for immunostaining. (a) Direct immunostaining for human Ig (hIg, left panels), showing localization of human antibodies to the epidermis after PF Ig passive transfer. The same tissue was immunostained with Flag antibodies, demonstrating the presence of Dsg2-Flag in the Tg, but not WT, skin (middle panels). Double labeling for the human Ig (red) and the Flag tag (green) is shown (right panels). Staining of human Ig was considerably more intact at the cell-cell border in the Tg skin, particularly in the superficial epidermis, where Dsg2 was expressed. Thus, superficial Dsg2 retains PF Ig at the cell-cell borders. (b) Lesional and nonlesional back skin sections were then immunostained with antibodies AP61, AP498, and Ab15, which were raised against the extracellular domain of Dsg1-, Dsg1-, and Dsg1-, respectively. DAPI (blue) was used as a nuclear stain. Arrows demarcate site of blister cleavage (lesional skin). In WT mice, treatment with PF Ig dramatically disrupted cell-cell border staining of Dsg1- and Dsg1- but not Dsg1- (left panels). Superficial expression of Dsg2 reduced the extent of Dsg1 perturbation (internalization and degradation). There was no significantly observable difference between lesional and non-lesional epidermis.
