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Investigation of the cellular metabolic pathways of immune cells, or immunometabolism, is a field of increasing interest. An understanding of immunometabolism provides routes to modifying T cell function for therapeutic purposes. Here, we review immunometabolism with a specific focus on regulatory T cells (Tregs). While T cells are known to switch their metabolic profile from oxidative phosphorylation to aerobic glycolysis upon activation, in vitro-induced Tregs display alternate metabolic characteristics which may be related to their specialised suppressive function. Recent data suggest that the preferential pathways employed by Tregs differ in vivo and ex vivo. Metabolic 'harshness', particularly the deterioration of glycolysis, positively affects Treg differentiation and function, while negatively correlating with Treg clonal expansion and migratory capacity. These context-dependent findings provide new insights into the behaviour of Tregs with implications for both tumour immunology and autoimmunity. This review examines the field in detail, offering an overview of our current understanding of Treg immunometabolism., (Copyright © 2020 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

Previous studies have shown that PLA-PEG nanoparticles (NP) are able to enhance the transport of the encapsulated model protein, tetanus toxoid (TT), across the rat nasal mucosa. The aim of this work was to study if the size of PLA-PEG particles affects the nasal transport of the encapsulated protein and, also, the potential contribution of blank nanoparticles to the transport of the free protein. To achieve this purpose, 125I-TT was encapsulated into PLA-PEG particles of different sizes (200 nm, 1.5, 5 and 10 microm) prepared by the water-in-oil-in-water solvent evaporation technique. Firstly, in order to investigate the carrier role of the particles, two series of either conscious or anaesthetized rats were nasally treated with 125I-TT-loaded NP, free 125I-TT, and a physical mixture of blank NP and free 125I-TT. Secondly, the influence of the particle size on the nasal transport of TT encapsulated into PLA-PEG particles was evaluated in conscious rats. The amount of radioactivity recovered in the blood compartment, lymph nodes and other relevant tissues was monitored for up to 24h. Finally, the nasal bioavailability of 125I-TT-loaded PLA-PEG NP was calculated. The results indicated that the use of anaesthesia enhances the transport of 125I-TT and that the physical presence of PLA-PEG NP does not affect the transport of the toxoid. In contrast, when TT was encapsulated into the particles its transport across the nasal mucosa of conscious rats was significantly enhanced. Furthermore, the efficacy of this transport was related to the particle size, reaching the most important transport for the smallest particle size. The intensity of this transport was also illustrated by the high nasal bioavailability of TT encapsulated into nanoparticles (200 nm) (F = 70-80%). These results led us to conclude that PLA-PEG NP can be accepted as nasal protein carriers for nasal administration.