Synthetic 5-amino-6-D-ribitylaminouracil paired with inflammatory stimuli facilitates MAIT cell expansion in vivo.

Introduction: Mucosal-associated invariant T (MAIT) cells are a population of innate-like T cells, which mediate host immunity to microbial infection by recognizing metabolite antigens derived from microbial riboflavin synthesis presented by the MHC-I-related protein 1 (MR1). Namely, the potent MAIT cell antigens, 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU) and 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil (5-OE-RU), form via the condensation of the riboflavin precursor 5-amino-6-D-ribitylaminouracil (5-A-RU) with the reactive carbonyl species (RCS) methylglyoxal (MG) and glyoxal (G), respectively. Although MAIT cells are abundant in humans, they are rare in mice, and increasing their abundance using expansion protocols with antigen and adjuvant has been shown to facilitate their study in mouse models of infection and disease. Methods: Here, we outline three methods to increase the abundance of MAIT cells in C57BL/6 mice using a combination of inflammatory stimuli, 5-A-RU and MG. Results: Our data demonstrate that the administration of synthetic 5-A-RU in combination with one of three different inflammatory stimuli is sufficient to increase the frequency and absolute numbers of MAIT cells in C57BL/6 mice. The resultant boosted MAIT cells are functional and can provide protection against a lethal infection of Legionella longbeachae. Conclusion: These results provide alternative methods for expanding MAIT cells with high doses of commercially available 5-A-RU (± MG) in the presence of various danger signals.

Breviscapine Alleviates Cognitive Impairments Induced by Transient Cerebral Ischemia/Reperfusion through Its Anti-Inflammatory and Anti-Oxidant Properties in a Rat Model.

Cerebral ischemia/reperfusion (I/R)-induced injury is a common phenomenon of stroke, and the effective treatment for I/R-induced brain tissue damage is limited. Breviscapine has been widely used in China as herbal medicine to treat cardiovascular diseases for hundreds of years and has been demonstrated to possess potent cardiovascular pharmacological effects. This study aims to investigate the neuroprotective effect of breviscapine on cerebral I/R-induced injury. The rat model of middle cerebral artery occlusion (MCAO) was applied in our study. The cerebral I/R rats received multiple injections of breviscapine. All rats were subject to neurological behavior tests by open field test and Morris water maze test. The pro-inflammatory cytokines and oxidative stress marker levels were determined by ELISA and colorimetric analysis, respectively. We demonstrated that administration of breviscapine dose-dependently ameliorated cerebral I/R-induced injury and improved the neurological performance of cerebral I/R rats. Further studies illustrated that breviscapine treatment effectively attenuated inflammatory cytokine expression, reduced oxidative stress, and pro-apoptosis protein expression and inhibited the activation of NF-κB signaling and microglia in the I/R injury tissues. Breviscapine may serve as a single drug or a promising adjuvant that can be used in conjunction with other medicine for the treatment of cerebral I/R-induced injury.