Xiaoyan Wu

Bio: Xiaoyan Wu is an academic researcher from South China Agricultural University. The author has contributed to research in topics: Cell signaling & Macrophage polarization. The author has co-authored 1 publications.

Glycinergic Signaling in Macrophages and Its Application in Macrophage-Associated Diseases.

Abstract: Accumulating evidences support that amino acids direct the fate decision of immune cells. Glycine is a simple structural amino acid acting as an inhibitory neurotransmitter. Besides, glycine receptors as well as glycine transporters are found in macrophages, indicating that glycine alters the functions of macrophages besides as an inhibitory neurotransmitter. Mechanistically, glycine shapes macrophage polarization via cellular signaling pathways (e.g., NF-κB, NRF2, and Akt) and microRNAs. Moreover, glycine has beneficial effects in preventing and/or treating macrophage-associated diseases such as colitis, NAFLD and ischemia-reperfusion injury. Collectively, this review highlights the conceivable role of glycinergic signaling for macrophage polarization and indicates the potential application of glycine supplementation as an adjuvant therapy in macrophage-associated diseases.

1H-NMR-Based Metabolomics in Autism Spectrum Disorder and Pediatric Acute-Onset Neuropsychiatric Syndrome

Abstract: We recently described a unique plasma metabolite profile in subjects with pediatric acute-onset neuropsychiatric syndrome (PANS), suggesting pathogenic models involving specific patterns of neurotransmission, neuroinflammation, and oxidative stress. Here, we extend the analysis to a group of patients with autism spectrum disorder (ASD), as a consensus has recently emerged around its immune-mediated pathophysiology with a widespread involvement of brain networks. This observational case-control study enrolled patients referred for PANS and ASD from June 2019 to May 2020, as well as neurotypical age and gender-matched control subjects. Thirty-four PANS outpatients, fifteen ASD outpatients, and twenty-five neurotypical subjects underwent physical and neuropsychiatric evaluations, alongside serum metabolomic analysis with 1H-NMR. In supervised models, the metabolomic profile of ASD was significantly different from controls (p = 0.0001), with skewed concentrations of asparagine, aspartate, betaine, glycine, lactate, glucose, and pyruvate. Metabolomic separation was also observed between PANS and ASD subjects (p = 0.02), with differences in the concentrations of arginine, aspartate, betaine, choline, creatine phosphate, glycine, pyruvate, and tryptophan. We confirmed a unique serum metabolomic profile of PANS compared with both ASD and neurotypical subjects, distinguishing PANS as a pathophysiological entity per se. Tryptophan and glycine appear as neuroinflammatory fingerprints of PANS and ASD, respectively. In particular, a reduction in glycine would primarily affect NMDA-R excitatory tone, overall impairing downstream glutamatergic, dopaminergic, and GABAergic transmissions. Nonetheless, we found metabolomic similarities between PANS and ASD that suggest a putative role of N-methyl-D-aspartate receptor (NMDA-R) dysfunction in both disorders. Metabolomics-based approaches could contribute to the identification of novel ASD and PANS biomarkers.

α-Aminobutyric Acid Constrains Macrophage-Associated Inflammatory Diseases through Metabolic Reprogramming and Epigenetic Modification

Abstract: Metabolites play critical roles in macrophage polarization and in their function in response to infection and inflammation. α-aminobutyric acid (AABA), a non-proteinogenic amino acid which can be generated from methionine, threonine, serine, and glycine, has not been studied extensively in relation to macrophage polarization and function. In this study, we aimed to investigate the immunomodulatory function of AABA in regulating M1 macrophage polarization and function in vitro and in vivo. We stimulated bone-marrow-derived macrophages with lipopolysaccharide (LPS) to generate M1 macrophages. Subsequently, we induced sepsis and colitis in mice, followed by treatment with AABA. We then analyzed the samples using ELISA, real-time PCR, Western blotting, flow cytometry, and histopathological analysis to evaluate cytokine secretion, inflammatory gene expression, macrophage activation, disease progression, and inflammation severity. Additionally, metabolomic and chromatin immunoprecipitation-qPCR were conducted to investigate the function of AABA on metabolic reprogramming and epigenetic modifications of M1 macrophages. Our results revealed that AABA inhibited M1 macrophage polarization and function, which led to prolonged survival in septic mice and reduced disease severity in colitis mice. Mechanically, AABA promoted oxidative phosphorylation (OXPHOS) and glutamine and arginine metabolism while inhibiting glycolysis. Moreover, AABA could increase the occupancy of trimethylation of histone H3K27 at the promoter regions of M1 macrophage-associated inflammatory genes, which contributed to the inhibition of M1 macrophage polarization. These findings suggest that AABA may have therapeutic potential for inflammatory diseases by regulating macrophage polarization and function through metabolic and epigenetic pathways.