Summary Interleukin (IL)-23 and CD4+ T helper-17 (Th17) cells are thought to be critical in the development of psoriasis. Here, we report that IL-23 predominantly stimulated dermal γδT cells to produce IL-17 that led to disease progression. Dermal γδT cells constitutively expressed the IL-23 receptor (IL-23R), RORγt, and various chemokine receptors. IL-17 production from dermal γδT cells was independent of αβT cells. The epidermal hyperplasia and inflammation induced by IL-23 were significantly decreased in T cell receptor δ deficient (Tcrd−/−) and IL-17 receptor deficient (Il17ra−/−) mice but occurred normally in Tcra−/− mice. Imiquimod-induced skin pathology was also significantly decreased in Tcrd−/− mice. Perhaps further promoting disease progression, IL-23 stimulated dermal γδT cell expansion. In psoriasis patients, γδT cells were also greatly increased in affected skin and produced large amounts of IL-17. Thus, IL-23-responsive dermal γδ T cells are the major IL-17 producers in the skin and may represent a novel target for the treatment of psoriasis.

Summary The gut microbiota can be altered by dietary interventions to prevent and treat various diseases. However, the mechanisms by which food products modulate commensals remain largely unknown. We demonstrate that plant-derived exosomes-like nanoparticles (ELNs) are taken up by the gut microbiota and contain RNAs that alter microbiome composition and host physiology. Ginger ELNs (GELNs) are preferentially taken up by Lactobacillaceae in a GELN lipid-dependent manner and contain microRNAs that target various genes in Lactobacillus rhamnosus (LGG). Among these, GELN mdo-miR7267-3p-mediated targeting of the LGG monooxygenase ycnE yields increased indole-3-carboxaldehyde (I3A). GELN RNAs or I3A, a ligand for aryl hydrocarbon receptor (AHR), are sufficient to induce production of IL-22, which is linked to barrier function improvement. These functions of GELN RNAs can ameliorate mouse colitis via IL-22-dependent mechanisms. These findings reveal how plant products and their effects on the microbiome may be used to target specific host processes to alleviate disease.

The importance of gut microbiota in human health and pathophysiology is undisputable. Despite the abundance of metagenomics data, the functional dynamics of gut microbiota in human health and disease remain elusive. Urolithin A (UroA), a major microbial metabolite derived from polyphenolics of berries and pomegranate fruits displays anti-inflammatory, anti-oxidative, and anti-ageing activities. Here, we show that UroA and its potent synthetic analogue (UAS03) significantly enhance gut barrier function and inhibit unwarranted inflammation. We demonstrate that UroA and UAS03 exert their barrier functions through activation of aryl hydrocarbon receptor (AhR)- nuclear factor erythroid 2–related factor 2 (Nrf2)-dependent pathways to upregulate epithelial tight junction proteins. Importantly, treatment with these compounds attenuated colitis in pre-clinical models by remedying barrier dysfunction in addition to anti-inflammatory activities. Cumulatively, the results highlight how microbial metabolites provide two-pronged beneficial activities at gut epithelium by enhancing barrier functions and reducing inflammation to protect from colonic diseases.

Evidence for a link between gut microbiota and hypertension in the Dahl rat. Physiol Genomics 47: 187-197, 2015. First published March 31, 2015 doi:10.1152/physiolgenomics.00136.2014.-The gut microbiota plays a critical role in maintaining physiological homeostasis. This study was designed to evaluate whether gut microbial composition affects hypertension. 16S rRNA genes obtained from cecal samples of Dahl salt-sensitive (S) and Dahl salt-resistant (R) rats were sequenced. Bacteria of the phylum Bacteroidetes were higher in the S rats compared with the R rats. Furthermore, the family S24-7 of the phylum Bacteroidetes and the family Veillonellaceae of the phylum Firmicutes were higher in the S rats compared with the R rats. Analyses of the various phylogenetic groups of cecal microbiota revealed significant differences between S and R rats. Both strains were maintained on a high-salt diet, administered antibiotics for ablation of microbiota, transplanted with S or R rat cecal contents, and monitored for blood pressure (BP). Systolic BP of the R rats remained unaltered irrespective of S or R rat cecal transplantation. Surprisingly, compared with the S rats given S rat cecal content, systolic BP of the S rats given a single bolus of cecal content from R rats was consistently and significantly elevated during the rest of their life, and they had a shorter lifespan. A lower level of fecal bacteria of the family Veillonellaceae and increased plasma acetate and heptanoate were features associated with the increased BP observed in the S rats given R rat microbiota compared with the S rats given S rat microbiota. These data demonstrate a link between microbial content and BP regulation and, because the S and R rats differ in their genomic composition, provide the necessary basis to further examine the relationship between the host genome and microbiome in the context of BP regulation in the Dahl rats. gut; microbial; SCFA; metabolic; metabolomics THE MAINTENANCE OF blood pressure (BP) homeostasis is a complex process that is carefully orchestrated by a variety of genetic and environmental factors and studied extensively in rat models (2, 5, 11, 15-17, 19, 21-23, 26, 42-44, 50). Dietary salt is one of the prominent environmental factors influencing the development and progression of salt-sensitive hypertension (13,14,24,57). As the consumed salt is transported through the gastrointestinal tract, one of the anatomical sites through which it is absorbed, in addition to the small intestine and the colon, is the cecum. The functions of the cecum are to absorb fluids and salts that remain after completion of intestinal digestion and absorption and to mix its contents with a lubricating substance, mucus. The cecum is also an "anerobic fermentor" as it houses a large number of bacteria that aid in digestion of undigested material in the stomach and small intestine. This is accomplished by a fermentative process that helps in breaking down fibers for their survival (33).In recent years, there is ample evidence in the literature ...

On line 8, gd was wrong. It should've read ''.T cells was independent of ab T cells.'' On line 10, d was omitted. It should've read ''.significantly decreased in T cell receptor d-deficient.'' On line 12, Il17ra -/was wrong. It should've read ''.occurred normally in Tcra À/À mice.'' On line 14, Il17ra -/was wrong. It should've read ''.decreased in Tcrd À/À mice.''The authors are sorry for any confusion this may have caused.Additionally, the Note Added in Proof published with this paper online on October 6, 2011 contained the following sentence: ''After acceptance of this manuscript, two studies were published describing a similar population of dermal gd T cells.'' The sentence should've read: ''During review of this manuscript, two studies were published describing a similar population of dermal gd T cells.'' We apologize for any confusion this may have caused.