TP A4: Mouse models of anti-laminin 332 mucous membrane pemphigoid: phenotypic characterization and pharmacological influence

Mucous membrane pemphigoid (MMP) is an immunobullous disease with autoantibodies against components of the dermal-epidermal-junction and a predominant mucosal involvement. One third of affected MMP patients show reactivity against laminin-332 and 25% of these patients develop a malignant tumor. Recently, an antibody transfer-induced mouse model for anti-laminin 332 MMP has been established in our group in adult mice, which reflects major clinical and immunopathological characteristics of human anti-laminin 332 MMP.

Distinct clarifications of the novel mouse model including the elucidation of inflammatory response during the pathogenesis, determination of specific cell types and signaling pathways, which are involved in pathogenesis, as well as the determination of the disease-inducing laminin 332 fragment, are the first steps within this project. Subsequently, possible distinctive cytokines/chemokines can be inhibited in the mouse model to study the impact on the disease process. Furthermore, a possible transferability can be ascertained between the new anti-laminin 332 MMP mouse model and the human MMP by determination of the degree of correspondence. The latter will form the basis for further and more accurate tests that may assist in the investigation of pathological mechanisms and in the future treatment of MMP. This point is critical, because so far the treatment of anti-laminin 332 MMP is unspecific and associated with side effects.