Melatonin affects a variety of physiological processes including circadian rhythms, cellular redox status, and immune function. Importantly, melatonin significantly influences T‐cell‐mediated immune responses, which are crucial to protect mammals against cancers and infections, but are associated with pathogenesis of many autoimmune diseases. This review focuses on our current understanding of the significance of melatonin in T‐cell biology and the beneficial effects of melatonin in T‐cell response‐based diseases. In addition to expressing both membrane and nuclear receptors for melatonin, T cells have the four enzymes required for the synthesis of melatonin and produce high levels of melatonin. Meanwhile, melatonin is highly effective in modulating T‐cell activation and differentiation, especially for Th17 and Treg cells, and also memory T cells. Mechanistically, the influence of melatonin in T‐cell biology is associated with membrane and nuclear receptors as well as receptor‐independent pathways, for example, via calcineurin. Several cell signaling pathways, including ERK1/2‐C/EBPα, are involved in the regulatory roles of melatonin in T‐cell biology. Through modulation in T‐cell responses, melatonin exerts beneficial effects in various inflammatory diseases, such as type 1 diabetes, systemic lupus erythematosus, and multiple sclerosis. These findings highlight the importance of melatonin signaling in T‐cell fate determination, and T cell‐based immune pathologies.

Currently, little is known about the function of arginine in the homeostasis of the intestinal immune system. This study was conducted to test the hyp

Enterotoxigenic Escherichia coli (ETEC) causes diarrhea in humans, cows, and pigs. The gut microbiota underlies pathology of several infectious diseases yet the role of the gut microbiota in the pathogenesis of ETEC-induced diarrhea is unknown. By using an ETEC induced diarrheal model in piglet, we profiled the jejunal and fecal microbiota using metagenomics and 16S rRNA sequencing. A jejunal microbiota transplantation experiment was conducted to determine the role of the gut microbiota in ETEC-induced diarrhea. ETEC-induced diarrhea influenced the structure and function of gut microbiota. Diarrheal piglets had lower Bacteroidetes: Firmicutes ratio and microbiota diversity in the jejunum and feces, and lower percentage of Prevotella in the feces, but higher Lactococcus in the jejunum and higher Escherichia-Shigella in the feces. The transplantation of the jejunal microbiota from diarrheal piglets to uninfected piglets leaded to diarrhea after transplantation. Microbiota transplantation experiments also supported the notion that dysbiosis of gut microbiota is involved in the immune responses in ETEC-induced diarrhea. We conclude that ETEC infection influences the gut microbiota and the dysbiosis of gut microbiota after ETEC infection mediates the immune responses in ETEC infection.

This study was conducted to investigate serum amino acids profile in dextran sulfate sodium (DSS)-induced colitis, and impacts of graded dose of arginine or glutamine supplementation on the colitis. Using DSS-induced colitis model, which is similar to human ulcerative colitis, we determined serum profile of amino acids at day 3, 7, 10 and 12 (5 days post DSS treatment). Meanwhile, effects of graded dose of arginine (0.4%, 0.8%, and 1.5%) or glutamine (0.5%, 1.0% and 2.0%) supplementation on clinical parameters, serum amino acids, colonic tight junction proteins, colonic anti-oxidative indicators [catalase, total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px)], colonic pro-inflammatory cytokines [interleukin-1 beta (IL-1β), IL-6, IL-17 and tumor necrosis factor alpha (TNF-α)] in DSS-induced colitis were fully analyzed at day 7 and 12. Additionally, the activation of signal transduction pathways, including nuclear factor kappa B (NF-κB), mitogen-activated protein kinases (MAPK), phosphoinositide-3-kinases (PI3K)/PI3K-protein kinase B (Akt), and myosin light chain kinase (MLCK)- myosin light chain (MLC20), were analyzed using immunoblotting. Serum amino acids analysis showed that DSS treatment changed the serum contents of amino acids, such as Trp, Glu, and Gln (P<0.05). Dietary arginine or glutamine supplementation had significant (P<0.05) influence on the clinical and biochemical parameters (T-SOD, IL-17 and TNF-α) in colitis model. These results were associated with colonic NF-κB, PI3K-Akt and MLCK signaling pathways. In conclusion, arginine or glutamine could be a potential therapy for intestinal inflammatory diseases.