Understanding CD4⁺ T cells in autoimmune bullous diseases

Autoimmune bullous diseases (AIBDs) are a group of life-threatening blistering diseases caused by autoantibodies that target proteins in the skin and mucosa. Autoantibodies are the most important mediator in the pathogenesis of AIBDs, and various immune mechanisms contribute to the production of these pathogenic autoantibodies. Recently, significant progress has been made in understanding how CD4⁺ T cells drive autoantibody production in these diseases. Here, we review the critical role of CD4⁺ T cells in the production of pathogenic autoantibodies for the initiation and perpetuation of humoral response in AIBDs. To gain an in-depth understanding of CD4⁺ T-cell pathogenicity, antigen specificity, and mechanisms of immune tolerance, this review covers comprehensive mouse and human studies of pemphigus and bullous pemphigoid. Further exploration of pathogenic CD4⁺ T cells will potentially provide immune targets for improved treatment of AIBDs.