This current review explores selected and as yet insufficiently investigated frontiers in current alopecia areata (AA) pathobiology research, with an emphasis on potential ''new'' players in AA pathobiology that deserve more systematic exploration and therapeutic targeting. Indeed, new evidence suggests that CD8 1 T cells, which have long been thought to be the central players in AA pathobiology, are not the only drivers of disease. Instead, subsets of natural killer (NK) and so-called ''unconventional'' T cells (invariant NK T cells, gd T cells, classic NK cells, and type 1 innate lymphoid cells), all of which can produce large amounts of IFN-g, might also drive AA pathobiology independent of classical, autoantigen-dependent CD8 1 T-cell functions. Another important new frontier is the role of regulatory lymphocyte subsets, such as regulatory T cells, gd regulatory T cells, NKT10 cells, and perifollicular mast cells, in maintaining physiologic hair follicle immune privilege (IP); the extent to which these functions are defective in patients with AA; and how this IP-protective role could be restored therapeutically in patients with established AA. Broadening our AA research horizon along the lines suggested above promises not only to open the door to innovative and even more effective immunotherapy strategies for AA but will also likely be relevant for other autoimmune disorders in which pathobiology, ectopic MHC class I expression, and IP collapse play an important role.

Autoimmune blistering diseases comprise a group of heterogenous conditions characterized by the loss of tolerance and subsequent development of autoantibodies targeting epidermal and subepidermal adhesion proteins. Blisters and erosions form on the skin and mucous membranes leading to significant morbidity and mortality. Traditional therapies rely on systemic immunosuppression. Advancements in our understanding of the pathophysiology of pemphigus and pemphigoid have led to the development of molecules which target specific pathways involved in induction and perpetuation of disease. In this review, we outline the novel therapeutic strategies including B‐cell depletion, T‐regulatory cell repletion, cell signalling inhibitors and small molecular inhibitors, inhibitory monoclonal antibodies, as well as complement inhibition. We additionally review their current level of clinical evidence. We lastly review therapeutics targets gleaned from the experimental epidermolysis bullosa acquisita mouse model. These emerging treatments offer an exciting progression from basic science discoveries that have the potential to transform the treatment paradigm in autoimmune blistering diseases.

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