In BP patients with mucosal involvement, skin and mucosal lesions are likely to concomitantly occur during the disease process. Although our results showed that mucosal involvement in BP was associated with disease severity, we also observed mucosal involvement in BP patient with mild disease. Actually, there was a broad distribution of total BPDAI score among BP patients with mucosal involvement, but the percentage of patients with mucosal involvement increased along with the BPDAI values (Figure 1C). This suggests that mucous membrane involvement in patients with mild BP is not just a consequence of the extent or severity of the disease, and therefore that some BP patients are more prone to develop mucosal lesions than others. Thus, we can speculate that specific biological/immunological mechanisms responsible for these lesions are activated in those BP patients. This further raised the question of the event on which a break of tolerance outside of the skin tissue could originate. Occurrence of mucosal lesions in some patients with BP recalls the variation in the number of sites involved in patients with mucous membrane pemphigoid (37). Previous study suggested that regulatory T (Treg) cells play an indispensable role in maintaining self-tolerance in BP leading to an increase in autoreactive Th2, Th1, and B cells that can recognize different domains of BP180 (38–40). The role of Treg cells in pemphigoid diseases was further demonstrated by mean of mice models (41). Although Treg cells account for less than 10% of peripheral CD4+ T cells, recent studies have reported that tissue resident Treg cells can even control non-immunological processes. Both Treg types demonstrated plasticity and can convert to Th17 cells according to the cytokine environment (42). In this line, we and other groups demonstrated the presence of cytokines such as IL-1, IL-6, IL-23, TGFβ, etc, in BP skin lesions. We also demonstrated that the cytokines panel more likely originated from BP epiphenomenon that still remained to be elucidated (26). Such variations could account for variations in a deficit in Treg cells and favor the development of tissue damages. In turn, skin remodeling could impact on both the number and the Treg homing at different levels of the skin compartments. Although aging has been associated with a loss of central immune tolerance in elderly patients as in BP (43), further investigations are now required to determine the events specifically responsible for the mucosal involvement in patients with BP, especially of the oral cavity.