Skin-homing interleukin-4 and-13-producing cells contribute to bullous pemphigoid: Remission of disease is associated with increased frequency of interleukin-10-producing cells

Although evidence is accumulating that type 2 cytokines play a part in the pathogenesis of bullous pemphigoid, little information is available concern ing characterization of the cellular source of these cytokines involved in the pathogenesis of bullous pemphigoid. By using multiparameter flow cytome try, we investigated T cells capable of producing interleukin-2, -4, -10, a nd -13, interferon-gamma, and tumor necrosis factor-a and their correlated expression of skin-homing receptor (cutaneous lymphocyte-associated antigen ) in peripheral blood and skin blister of patients with bullous pemphigoid. In peripheral blood of bullous pemphigoid patients, significantly increase d frequencies of interleukin-gamma and interleukin-13-producing cells were found as compared with those of healthy controls, and the majority of these type 2 cells was found in the cutaneous lymphocyte-associated antigen-posi tive population. The frequency of interferon-gamma -producing cells was als o increased as compared with healthy subjects; however, the majority of thi s subset was found in the cutaneous lymphocyte-associated antigen-negative population. In the skin blister, the frequencies of interieukin-13- and int erleukin-4-producing cells were much higher than those in the peripheral bl ood of bullous pemphigoid, whereas that of interferon-gamma producing cells was significantly lower. Furthermore, in bullous pemphigoid patients after therapy with systemic corticosteroids, the frequency of cutaneous lymphocy te-associated antigen-positive, but not cutaneous lymphocyte-associated ant igen-negative, interleukin-13-producing cells was significantly decreased a ccompanied by an increased frequency of interleukin-10-producing cells, whi ch was associated with clinical improvement. Thus, our results suggest that bullous pemphigoid is a unique organ-specific autoimmune disease character ized by an expansion of skin-homing interleukin-13-producing cells. In addi tion, corticosteroids may control such type 2 biased inflammatory responses in bullous pemphigoid by promoting the expansion of interleukin-10-produci ng cells.