T-cell/B-cell interactions are a central component in the pathogenesis of all antibody-mediated auto-immune diseases. This usually take place in secondary lymphoid organs (SLO) where follicular T helper (Tfh) cells drive the differentiation of B cells into high-affinity antibody-secreting cells. Interestingly, similar reactions can also occur directly in inflamed non-lymphoid tissues. There, the recently described CD4+ T cell population of peripheral T helper (Tph) cells shares numerous features with Tfh cells, including their ability to provide B cell help. Unlike Tfh cells, which interact with B cells in the highly organised environment of SLO, Tph cells reside in unstructured T cell / B cell infiltrates in the inflamed tissue. This uncontrolled T/B cell interaction poses a high risk for the formation of auto-reactive antibodies. In addition, the tissue-resident inflammatory B cells have a particular phenotype characterised by expression of the transcription factor T-bet.

Pemphigoid diseases (PDs) such as bullous pemphigoid (BP) and epidermolysis bullosa acquisita (EBA) are prototypical autoantibody-driven diseases. However, how the autoantibodies are formed is still largely unclear. Besides cells of the innate immune system, T and B cells are also abundant in the skin lesions of PDs patients. However, their contribution to pathogenesis has not yet been explored in detail. Our preliminary data suggest that peripheral T helper (Tph) cells and T-bet+ B cells are highly proliferated in the peripheral blood of BP patients and that T cells interact directly with B cells in lymphoid infiltrates in the skin.

The influence of novel T cell populations, i.e., Tfh and Tph cells, on autoantibody-mediated inflammatory skin diseases is investigated in the EBA immunisation-induced mouse model. To this end, we aim to develop a new therapeutic approach for such diseases by modulating Tfh and Tph cells and their functions.