The role of lymphocyte-derived Factors in the effector phase of pemphigoid diseases
Pemphigoid diseases (PD) are initiated by the production of autoantibodies to skin antigens, later the effector phase of PDs is driven by the influx of myeloid cells, particularly neutrophils, into the skin. Our previous results uncovered a network of various lymphocyte populations, innate lymphocytes, Tregs, and IL-10+ plasma cells, regulating the recruitment of PMNs, their activation, and, consequently, skin inflammation from the emergence of inflammatory skin lesions to their resolution in mouse models of PD. While innate lymphocytes facilitate the influx of neutrophils into the skin and activate them, especially in early stages of the emergence of PD skin lesions, while Tregs and IL-10+ plasma cells, in contrast, counteract and contain PD skin inflammation, in significant parts by the release of IL-10. Intriguingly, we have also highlighted that this network of lymphocytes can be manipulated. Particularly, the induction of IL-10+ plasma cells is effective in ameliorating disease. Plasma cell-derived IL-10 was found to inhibit neutrophil activity directly but also reinforced the release of IL-10 from Tregs. We have also found evidence that a corresponding network of lymphocyte populations also exist in bullous pemphigoid (BP) patients. These results suggest that different lymphocyte populations and their effector mechanisms are promising therapeutic targets in PDs. Particularly promoting IL-10+ plasma cells or Tregs, or application of IL-10 may constitute most effective therapeutic strategies to reverse PD skin inflammation with only few side effects. Here, we will further investigate the mode of action of IL-10 and of IL-10+ plasma cells in PDs. We will develop and evaluate strategies exploiting these mechanisms for therapeutic purposes in PDs.