Associated TP29: Effects of lymphocyte-derived IL-10 on the effector phase of epidermolysis bullosa acquisita

Epidermolysis bullosa acquisita (EBA) belongs to the group of autoimmune blistering skin diseases, which are all mediated by autoantibodies directed against adhesion molecules in the skin. EBA is characterized by autoantibodies targeting collagen type VII (Col7). Autoreactive plasma cells significantly contribute to the development of EBA via their production of autoantibodies but B cells/plasma cells are also able to modulate the disease via costimulatory molecules and cytokines. An important mechanism for suppressing autoimmune diseases include the production of the cytokine Interleukin-10 (IL-10).

Recent findings from our group demonstrated that terminal differentiated B cells (plasma cells) produce IL-10 and are able to completely inhibit the EBA inflammation (associated TP2, Kulkarni et al., J Allergy Clin Immunol, 2015). After polyclonal B cell activation, a plasmacytosis was induced and led to a massive IL-10 production by plasma cells. This in turn had the ability to significantly reduce the skin disease in the experimental EBA model for at least another 3-4 weeks connected to a strong reduction of neutrophil migration into the inflamed skin.

Based on our recent data, we expect that B cell/plasma cell IL-10 can control the onset and the severity of the EBA skin disease. So far, we don’t know if IL-10 displays the same effects during a normal EBA pathogenesis without an additional B cell activation and if the anti-inflammatory properties of IL-10 would be of therapeutic benefit. For our study, we want to use the active (Col7 immunization-induced) or the passive (anti-Col7 IgG autoantibody transfer-induced) experimental EBA mice model to distinguish between the complete EBA pathogenesis and only the effector phase, respectively.