CD8+ tissue-resident memory T (TRM) cells provide frontline immunity in mucosal tissues. The mechanisms regulating CD8+ TRM maintenance, heterogeneity, and protective and pathological functions are largely elusive. Here, we identify a population of CD8+ TRM cells that is maintained by major histocompatibility complex class I (MHC-I) signaling, and CD80 and CD86 costimulation after acute influenza infection. These TRM cells have both exhausted-like phenotypes and memory features and provide heterologous immunity against secondary infection. PD-L1 blockade after the resolution of primary infection promotes the rejuvenation of these exhausted-like TRM cells, restoring protective immunity at the cost of promoting postinfection inflammatory and fibrotic sequelae. Thus, PD-1 serves to limit the pathogenic capacity of exhausted-like TRM cells at the memory phase. Our data indicate that TRM cell exhaustion is the result of a tissue-specific cellular adaptation that balances fibrotic sequelae with protective immunity.

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Ginsenoside Rg3 (Rg3), a major active ingredient enriched in red ginseng, possesses well-confirmed immunoregulatory effects. Immune disturbance is a common trigger and aggravating factor of depression. The aim of this study was to explore the effects of Rg3 on lipopolysaccharide (LPS)-induced depression-like behavior in mice and the involvement of immune regulation. Pretreatment with Rg3 (i.g., 20 and 40 mg/kg) effectively ameliorated LPS (i.p., 0.83 mg/kg) induced body weight loss, anorexia, and immobility time in both the tail suspension test and the forced swimming test. Rg3 attenuated the disturbed turnover of tryptophan and serotonin in the hippocampus, accompanied by decreased mRNA expression of pro-inflammatory cytokines and indoleamine-2,3-dioxygenase (IDO). These central benefits were partially linked to the regulation of microglia activation and nuclear factor kappa B (NF-κB) pathway. In addition, Rg3 significantly reduced LPS-induced elevation of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in plasma, and restored the systemic balance of tryptophan-kynurenine metabolism. Taken together, our results demonstrated that Rg3 was effective in ameliorating depressive-like behavior induced by immune activation, adding new evidence to support its health benefits by immunoregulation.

Background and objective: Asthma is a global problem and complex disease suited for metabolomic profiling. This study explored the candidate biomarkers specific to paediatric asthma and provided insights into asthmatic pathophysiology. Methods: Children (aged 6-11 years) meeting the criteria for healthy control (n = 29), uncontrolled asthma (n = 37) or controlled asthma (n = 43) were enrolled. Gas chromatography-mass spectrometry was performed on urine samples of the patients to explore the different types of metabolite profile in paediatric asthma. Additionally, we employed a comprehensive strategy to elucidate the relationship between significant metabolites and asthma-related genes. Results: We identified 51 differential metabolites mainly related to dysfunctional amino acid, carbohydrate and purine metabolism. A combination of eight candidate metabolites, including uric acid, stearic acid, threitol, acetylgalactosamine, heptadecanoic acid, aspartic acid, xanthosine and hypoxanthine (adjusted P < 0.05 and fold-change >1.5 or <0.67), showed excellent discriminatory performance for the presence of asthma and the differentiation of poor-controlled or well-controlled asthma, and area under the curve values were >0.97 across groups. Enrichment analysis based on these targets revealed that the Fc receptor, intracellular steroid hormone receptor signalling pathway, DNA damage and fibroblast proliferation were involved in inflammation, immunity and stress-related biological progression of paediatric asthma. Conclusion: Metabolomic analysis of patient urine combined with network-biology approaches allowed discrimination of asthma profiles and subtypes according to the metabolic patterns. The results provided insight into the potential mechanism of paediatric asthma.We investigated metabolic profiles of paediatric asthma patients to identify asthma-specific biomarkers in urine. A combination of eight metabolites showed excellent discrimination across groups. Enrichment analysis identified complex biological processes associated with immunity, inflammation, oxidative stress and DNA damage. These approaches enabled discrimination between asthma stages and elucidate its mechanisms.