Our results provide evidence that IL-5-activated eosinophils directly contribute to BP blister formation in the presence of BP autoantibodies. Dermal-epidermal separation by IL-5-activated eosinophils depends on adhesion and Fcγ receptor activation, requires elevated ROS production and degranulation and involves EET formation. Thus, targeting eosinophils may be a promising therapeutic approach for BP.

We report that adhesion-induced eosinophil cytolysis takes place through RIPK3-MLKL-dependent necroptosis, which can be counterregulated by autophagy.

Our observations suggest that the interaction of cells, as shown here for monocytes and neutrophils, enhances mediator release resulting in an increased subepidermal blister formation. Thus, blocking intercellular cross talk promises a new therapeutic approach for blocking tissue damage in BP.

Key Points Repertoire analysis by microarray technology constitutes a powerful tool to evaluate immune system failure in PADs.