Depletion of regulatory T cells breaks self-tolerance and induces epidermolysis bullosa acquisita in resistant C57BL/6J mice.

Pemphigoid diseases (PDs) are antibody-mediated autoimmune blistering diseases caused by loss of tolerance to basement membrane proteins such as type VII collagen (COL7), triggering pathogenic T and B cell responses. The contribution of regulatory T cells (Tregs) to disease resistance remains unclear. Using a COL7 immunization-induced PD mouse model, we show that transient Treg depletion breaks tolerance and induces skin blistering in otherwise PD-resistant H2b mice. Disease occurred predominantly in females and was associated with impaired Treg recovery, early skin inflammation, altered B-cell homeostasis, and antigen-specific CD154+ T cells. These findings identify Tregs as critical regulators of susceptibility to PD.