Foxp3 regulatory T (Treg) cells, which suppress immune responses, are highly proliferative in vivo. However, it remains unclear how the active replication of Treg cells is maintained in vivo. Here, we show that branched-chain amino acids (BCAAs), including isoleucine, are required for maintenance of the proliferative state of Treg cells via the amino acid transporter Slc3a2-dependent metabolic reprogramming. Mice fed BCAA-reduced diets showed decreased numbers of Foxp3 Treg cells with defective in vivo proliferative capacity. Mice lacking Slc3a2 specifically in Foxp3 Treg cells showed impaired in vivo replication and decreased numbers of Treg cells. Slc3a2-deficient Treg cells showed impaired isoleucine-induced activation of the mTORC1 pathway and an altered metabolic state. Slc3a2 mutant mice did not show an isoleucine-induced increase of Treg cells in vivo and exhibited multi-organ inflammation. Taken together, these findings demonstrate that BCAA controls Treg cell maintenance via Slc3a2-dependent metabolic regulation.

Nutritional epidemiology shows that insufficient protein intake is related to senile dementia. The levels of protein intake in aged people are positively associated with memory function, and elderly people with high protein intake have a low risk of mild cognitive impairment. Although the beneficial roles of protein nutrition in maintaining brain function in aged people are well demonstrated, little is known about the mechanism by which dietary intake of protein affects memory and brain conditions. We fed aged mice a low protein diet (LPD) for 2 months, which caused behavioral abnormalities, and examined the nutritional effect of essential amino acid administration under LPD conditions. The passive avoidance test revealed that LPD mice demonstrated learning and memory impairment. Similarly, the LPD mice showed agitation and hyperactive behavior in the elevated plus maze test. Moreover, LPD mice exhibited decreased concentrations of gamma-aminobutyric acid (GABA), glutamate, glycine, dopamine, norepinephrine, serotonin and aspartate in the brain. Interestingly, oral administration of seven essential amino acids (EAAs; valine, leucine, isoleucine, lysine, phenylalanine, histidine, and tryptophan) to LPD mice, which can be a source of neurotransmitters, reversed those behavioral changes. The oral administration of EAAs restored the brain concentration of glutamate, which is involved in learning and memory ability and may be associated with the observed behavioral changes. Although the details of the link between decreased amino acid and neurotransmitter concentrations and behavioral abnormalities must be examined in future studies, these findings suggest the importance of dietary protein and essential amino acids for maintaining brain function.

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Aim To examine the association between depressive symptoms and plasma amino acid related metaboli in older adults. Methods A total of 152 older adults aged ≥65 years, residing in Niigata, Japan, were used for analysis. We evaluated depressive symptoms using the Geriatric Depression Scale‐15, which has been validated in older community‐dwelling individuals, and used a cut off score of ≥5 to classify participants as having depressive symptoms. We used high‐performance liquid chromatography‐electrospray ionization mass spectrometry to measure the concentrations of plasma amino acid‐related metabolites, and carried out logistic regression analysis to assess the association between depressive symptoms and plasma amino acid‐related metabolites. Results Of the 119 older adults (mean age 76.3 years) included in the analysis, 22 were classified as having depressive symptoms (depressive group). There were no significant differences in physical and cognitive impairments between participants in the depressive and non‐depressive groups. The plasma α‐aminobutyric acid (AABA) level was significantly lower in the depressive group than in the non‐depressive group (P < 0.001). Logistic regression analysis showed the best‐fit model, which included AABA, leucine, threonine, hydroxyl proline and histidine levels (area under the receiver operating characteristic curve 0.8346; 95% confidence interval 0.7365–0.9326). In particular, the plasma AABA level was strongly associated with depressive symptoms. Conclusions Plasma AABA level is significantly associated with depression symptoms in older community‐dwelling adults in Japan. Thus, plasma AABA might serve as a potential marker of depression in older adults aged ≥65 years. Geriatr Gerontol Int 2019; 19: 254–258.

We address the issue of appropriate user modeling to generate cooperative responses to users in spoken dialogue systems. Unlike previous studies that have focused on a user's knowledge, we propose more generalized modeling. We specifically set up three dimensions for user models: the skill level in use of the system, the knowledge level about the target domain, and the degree of urgency. Moreover, the models are automatically derived by decision tree learning using actual dialogue data collected by the system. We obtained reasonable accuracy in classification for all dimensions. Dialogue strategies based on user modeling were implemented on the Kyoto City Bus Information System that was developed at our laboratory. Experimental evaluations revealed that the cooperative responses adapted to each subject type served as good guides for novices without increasing the duration dialogue lasted for skilled users.