We investigated the anti-aging effects of Ludwigia octovalvis (Jacq.) P. H. Raven (Onagraceae), an extract of which is widely consumed as a healthful drink in a number of countries. Using the fruit fly, Drosophila melanogaster, as a model organism, we demonstrated that L. octovalvis extract (LOE) significantly extended fly lifespan on a high, but not a low, calorie diet, indicating that LOE may regulate lifespan through a dietary restriction (DR)-related pathway. LOE also attenuated age-related cognitive decline in both flies and in the senescence-accelerated-prone 8 (SAMP8) mouse, without causing any discernable negative trade-offs, including water intake, food intake, fecundity, or spontaneous motor activity. LOE contained high levels of polyphenols and flavonoids, which possess strong DPPH radical scavenging activity, and was shown to attenuate paraquat-induced oxidative damage and lethality in flies. Gas chromatography-mass spectrometry (GC-MS) analyses identified 17 known molecules, of which β-sitosterol and squalene were the two most abundant. We further demonstrated that β-sitosterol was capable of extending lifespan, likely through activating AMP-activated protein kinase (AMPK) in the fat body of adult flies. Taken together, our data suggest that LOE is a potent anti-aging intervention with potential for treating age-related disorders.

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Nociceptors, the high-threshold primary sensory neurons that trigger pain, interact with immune cells in the periphery to modulate innate immune responses. Whether they also participate in adaptive and humoral immunity is, however, not known. In this study, we probed if nociceptors have a role in distinct airway and skin models of allergic inflammation. In both models, the genetic ablation and pharmacological silencing of nociceptors substantially reduced inflammatory cell infiltration to the affected tissue. Moreover, we also found a profound and specific deficit in IgE production in these models of allergic inflammation. Mechanistically, we discovered that the nociceptor-released neuropeptide substance P helped trigger the formation of antibody-secreting cells and their release of IgE. Our findings suggest that nociceptors, in addition to their contributions to innate immunity, play a key role in modulating the adaptive immune response, particularly B cell antibody class switching to IgE.

Although air pollutants such as fine particulate matter (PM 2.5 ) are associated with acute and chronic lung inflammation, the etiology of PM 2.5 -induced airway inflammation remains poorly understood. Here we report that PM 2.5 triggered airway hyperreactivity (AHR) and neutrophilic inflammation with concomitant increases in Th1 and Th17 responses and epithelial cell apoptosis. We found that γδ T cells promoted neutrophilic inflammation and AHR through IL-17A. Unexpectedly, we found that invariant natural killer T (iNKT) cells played a protective role in PM 2.5 -induced pulmonary inflammation. Specifically, PM 2.5 activated a suppressive CD4 – iNKT cell subset that coexpressed Tim-1 and programmed cell death ligand 1 (PD-L1). Activation of this suppressive subset was mediated by Tim-1 recognition of phosphatidylserine on apoptotic cells. The suppressive iNKT subset inhibited γδ T cell expansion and intrinsic IL-17A production, and the inhibitory effects of iNKT cells on the cytokine-producing capacity of γδ T cells were mediated in part by PD-1/PD-L1 signaling. Taken together, our findings underscore a pathogenic role for IL-17A–producing γδ T cells in PM 2.5 -elicited inflammation and identify PD-L1 + Tim-1 + CD4 – iNKT cells as a protective subset that prevents PM 2.5 -induced AHR and neutrophilia by inhibiting γδ T cell function.