Group 2 innate lymphoid cells (ILC2s) represent innate homologs of type 2 helper T cells (TH2) that participate in immune defense and tissue homeostasis through production of type 2 cytokines. While T lymphocytes metabolically adapt to microenvironmental changes, knowledge of human ILC2 metabolism is limited, and its key regulators are unknown. Here, we show that circulating ‘naive’ ILC2s have an unexpected metabolic profile with a higher level of oxidative phosphorylation (OXPHOS) than natural killer (NK) cells. Accordingly, ILC2s are severely reduced in individuals with mitochondrial disease (MD) and impaired OXPHOS. Metabolomic and nutrient receptor analysis revealed ILC2 uptake of amino acids to sustain OXPHOS at steady state. Following activation with interleukin-33 (IL-33), ILC2s became highly proliferative, relying on glycolysis and mammalian target of rapamycin (mTOR) to produce IL-13 while continuing to fuel OXPHOS with amino acids to maintain cellular fitness and proliferation. Our results suggest that proliferation and function are metabolically uncoupled in human ILC2s, offering new strategies to target ILC2s in disease settings.
Distinct metabolic demands accompany lymphocyte differentiation into short-lived effector and long-lived memory cells. How bioenergetics processes are structured in innate natural killer (NK) cells remains unclear. We demonstrate that circulating human CD56Dim (NKDim) cells have fused mitochondria and enhanced metabolism compared with CD56Br (NKBr) cells. Upon activation, these 2 subsets showed a dichotomous response, with further mitochondrial potentiation in NKBr cells vs paradoxical mitochondrial fission and depolarization in NKDim cells. The latter effect impaired interferon-γ production, but rescue was possible by inhibiting mitochondrial fragmentation, implicating mitochondrial polarization as a central regulator of NK cell function. NKDim cells are heterogeneous, and mitochondrial polarization was associated with enhanced survival and function in mature NKDim cells, including memory-like human cytomegalovirus–dependent CD57+NKG2C+ subsets. In contrast, patients with genetic defects in mitochondrial fusion had a deficiency in adaptive NK cells, which had poor survival in culture. These results support mitochondrial polarization as a central regulator of mature NK cell fitness.
Mandibular fractures are the third most frequents maxillo-facial fractures. Most frequent site is the subcondylar region. Different approaches to reach subcondylar region, have been described. In the study was evaluated the advantages of neuromuscular block during endoscopic surgery for subcondylar fractures. Twenty-five patients affected by subcondylar fractures were enrolled in this study and divided in 2 groups; group A: patients who received an intraoperative booster of curare during surgical procedure and group B patients who underwent surgery treated without the intraoperative booster of curare. All patients were treated successfully by endoscope-assisted transoral approach. The analysis of time required for surgery showed a reduction in group A comparing to group B. The mean time for surgery for the patients in group B with displacement between 08 and 458 was 170 minutes, and for 458 to 908 was 230 minutes. In group A, the mean time was 117.5 minutes for patients with condylar displacement between 08 and 458, and 147.5 minutes for the other group. In conclusion, deep neuromuscular block seems to improve the surgical conditions in patients undergoing subcondylar endoscopic assisted surgery, further study needs to assess this surgical technique in order to better define this surgical protocol.
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