The frequency of SCA3/MJD is substantially higher than that of SCA1 and SCA2 in patients with autosomal dominant SCA from Chinese kindreds, who are non-Portuguese. Clinical expressions of the various types of SCAs overlap one another; therefore, for clinical study it is important to make a gene diagnosis and genetic classification for patients with SCA.

These findings suggest that graft-infiltrating PD-L1 CD-DCs may play a key role in the regulation of alloimmunity and in the induction of liver transplant tolerance. (Hepatology 2018;67:1499-1515).

temic expansion of ST2 + Tregs (29,30). IL-33 expressed by fibrogenic/adipogenic progenitors in skeletal muscle has also been shown to regulate skeletal muscle Treg homeostasis and support muscle regeneration (31). Related studies have suggested a direct, cardioprotective role for rIL-33 against hypertrophy resulting from cardiac overload (32) and fibrosis after myocardial infarction (33). However, delivery of rIL-33 also aggravates autoimmune eosinophilic pericarditis during coxsackievirus B3 infection (34), suggesting that IL-33 can contribute to cardiac inflammation. IL-33 expression has been reported in cardiac fibroblasts (32) and the vasculature ( 35), yet how the expression of this alarmin is modulated in cardiac allografts or impacts outcomes was unknown.Using IL-33-deficient heart grafts in a mouse chronic rejection model we have established that IL-33 stands out among identified alarmins and limits differentiation of proinflammatory macrophages to prevent chronic rejection. Specifically, transplants lacking IL-33 displayed dramatically accelerated chronic rejectionassociated vasculopathy and subsequent fibrosis orchestrated by graft-infiltrating recipient proinflammatory macrophages. IL-33expressing heart grafts in recipients with ST2-deficient macrophages also displayed increased graft infiltration by proinflammatory macrophages and accelerated graft loss. Mechanistic studies demonstrated that IL-33 promoted a reparative macrophage phenotype through a metabolic reprograming involving augmented oxidative phosphorylation (OXPHOS) and fatty acid (FA) uptake. We also revealed that IL-33 prevents proinflammatory stimuli-induced disruption of the tricarboxylic acid (TCA) cycle that shifts macrophage metabolism to anaerobic glycolysis and generates proinflammatory metabolites (36,37). Restoration of IL-33 to IL-33-deficient heart transplants using vesicles in ECM-derived hydrogel immediately after transplantation profoundly reduced the frequency of proinflammatory myeloid cells in the graft and prevented graft loss to chronic rejection. Thus, the local delivery of IL-33 in ECM-based materials after transplantation may be a practical and promising biologic for chronic rejection prophylaxis.

Regulatory dendritic cells (DCreg) promote transplant tolerance following their adoptive transfer in experimental animals. We investigated the feasibility, safety, fate, and impact on host T cells of donor monocyte‐derived DCreg infused into prospective, living donor liver transplant patients, 7 days before transplantation. The DCreg expressed a tolerogenic gene transcriptional profile, high cell surface programed death ligand‐1 (PD‐L1):CD86 ratios, high IL‐10/no IL‐12 productivity and poor ability to stimulate allogeneic T cell proliferation. Target DCreg doses (range 2.5–10 × 106 cells/kg) were achieved in all but 1 of 15 recipients, with no infusion reactions. Following DCreg infusion, transiently elevated levels of donor HLA and immunoregulatory PD‐L1, CD39, and CD73 were detected in circulating small extracellular vesicles. At the same time, flow and advanced image stream analysis revealed intact DCreg and “cross‐dressing” of host DCs in blood and lymph nodes. PD‐L1 co‐localization with donor HLA was observed at higher levels than with recipient HLA. Between DCreg infusion and transplantation, T‐bethiEomeshi memory CD8+ T cells decreased, whereas regulatory (CD25hiCD127−Foxp3+): T‐bethiEomeshi CD8+ T cell ratios increased. Thus, donor‐derived DCreg infusion may induce systemic changes in host antigen‐presenting cells and T cells potentially conducive to modulated anti‐donor immune reactivity at the time of transplant.

Improved survival following organ transplantation has brought to the forefront some long-term complications, among which osteoporosis and associated fractures are the major ones that adversely affect the quality of life in recipients. The pathogenesis of osteoporosis in transplant recipients is complex and multifactorial which may be related to increased bone resorption, decreased bone formation, or both. Studies have shown that the preexisting underlying metabolic bone disorders and the use of immunosuppressive agents are the major risk factors for osteoporosis and fractures after organ transplantation. And rapid bone loss usually occurs in the first 6–12 months with a significant increase in fracture risk. This paper will provide an updated review on the possible pathogenesis of posttransplant osteoporosis and fractures, the natural history, and the current prevention and treatment strategies concerning different types of organ transplantation.