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Cell death mechanisms in T lymphocytes vary according to their developmental stage, cell subset and activation status. The cell death control mechanisms of mucosal-associated invariant T (MAIT) cells, a specialized T cell population, are largely unknown. Here we report that MAIT cells express key necroptotic machinery; receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL) protein, in abundance. Despite this, we discovered that the loss of RIPK3, but not necroptotic effector MLKL or apoptotic caspase-8, specifically increased MAIT cell abundance at steady-state in the thymus, spleen, liver and lungs, in a cell-intrinsic manner. In contrast, over the course of infection with Francisella tularensis, RIPK3 deficiency did not impact the magnitude of the expansion nor contraction of MAIT cell pools. These findings suggest that, distinct from conventional T cells, the accumulation of MAIT cells is restrained by RIPK3 signalling, likely prior to thymic egress, in a manner independent of canonical apoptotic and necroptotic cell death pathways.

Bullous pemphigoid (BP) is an autoimmune blistering disease that commonly occurs in the elderly. Immunosuppressive medications are effective at controlling the disease in the majority of cases. Mortality can occur as a consequence of severe disease or as a result of the therapies that are frequently employed as treatment. Commonly employed therapies include systemic corticosteroids, azathioprine and mycophenolate mofetil. In a small subset of patients, these first- and second-line therapies do not control disease or are not tolerated by the patients. Optional therapies include nicotinamide (niacinamide), tetracycline, intravenous immunoglobulin, cyclophosphamide, dapsone and methotrexate. The majority of BP patients are elderly, and several considerations need to be taken into account before a specific therapy is chosen. Methotrexate provides several advantages in the elderly population in terms of practicality, cost and tolerability. Several retrospective and prospective studies have evaluated its effectiveness in the treatment of BP in the elderly population. The results of these studies indicate that methotrexate is an effective therapy for BP and is a reasonable option for treatment in the elderly population, although maybe not as a first- or second-line therapy.