D-mannose induces regulatory T cells and suppresses immunopathology.

D-mannose, a C-2 epimer of glucose, exists naturally in many plants and fruits, and is found in human blood at concentrations less than one-fiftieth of that of glucose. However, although the roles of glucose in T cell metabolism, diabetes and obesity are well characterized, the function of D-mannose in T cell immune responses remains unknown. Here we show that supraphysiological levels of D-mannose safely achievable by drinking-water supplementation suppressed immunopathology in mouse models of autoimmune diabetes and airway inflammation, and increased the proportion of Foxp3+ regulatory T cells (Treg cells) in mice. In vitro, D-mannose stimulated Treg cell differentiation in human and mouse cells by promoting TGF-ß activation, which in turn was mediated by upregulation of integrin αvß8 and reactive oxygen species generated by increased fatty acid oxidation. This previously unrecognized immunoregulatory function of D-mannose may have clinical applications for immunopathology.

Gut Microbiome Function Predicts Response to Anti-integrin Biologic Therapy in Inflammatory Bowel Diseases.

The gut microbiome plays a central role in inflammatory bowel diseases (IBDs) pathogenesis and propagation. To determine whether the gut microbiome may predict responses to IBD therapy, we conducted a prospective study with Crohn's disease (CD) or ulcerative colitis (UC) patients initiating anti-integrin therapy (vedolizumab). Disease activity and stool metagenomes at baseline, and weeks 14, 30, and 54 after therapy initiation were assessed. Community α-diversity was significantly higher, and Roseburia inulinivorans and a Burkholderiales species were more abundant at baseline among CD patients achieving week 14 remission. Several significant associations were identified with microbial function; 13 pathways including branched chain amino acid synthesis were significantly enriched in baseline samples from CD patients achieving remission. A neural network algorithm, vedoNet, incorporating microbiome and clinical data, provided highest classifying power for clinical remission. We hypothesize that the trajectory of early microbiome changes may be a marker of response to IBD treatment.

[Effect of Macrovipera lebetina and Cerastes cerastes venoms on adherence to integrins of cancerous cells (IGR39, HT29-D4 and IGROV1)]. / Effet des venins de Macrovipera lebetina et de Cerastes cerastes sur l'adherence aux intégrines des cellules cancéreuses (IGR39, HT29-D4 et IGROV1).

In this work, we provide experimental arguments in favor of the fact that components from Macrovipera lebetina and Cerastes cerastes venoms bind to IGR39 melanoma cells but not to HT29D4 cells that derive from carcinoma adenome. Furthermore, Macrovipera lebetina and Cerastes cerastes venoms inhibit the adherence of IGR39 and HT 29-D4 to various extracellular matrix proteins. Macrovipera lebetina and Cerastes cerastes venoms did not inhibit the non specific adherence of IGR 39 cells to polylysine. In addition, binding of components from Cerastes cerastes venom to IGR39 cells is inhibited by GRGDS peptide and by monoclonal antibidy anti-av, while these two components have no effect on the adherence of IGR39 to Macrovipera lebetina venom.

Frangulin B, an antagonist of collagen-induced platelet aggregation and adhesion, isolated from Rhamnus formosana.

Emodin and its glycoside frangulin B were isolated from the plant Rhamnus formosana. Emodin inhibited the aggregation of rabbit platelets induced by arachidonic acid and collagen, without affecting that by ADP or PAF, while emodin acetate had no any antiplatelet effect. Frangulin B inhibited selectively and concentration-dependently collagen-induced aggregation and ATP release in rabbit platelets, without affecting those induced by arachidonic acid, ADP, PAF and thrombin. Frangulin B also inhibited the platelet aggregation induced by trimucytin which was reported to be a collagen receptor agonist isolated from Trimeresurus muscrosquamatus snake venom. The aggregability of platelets inhibited by frangulin B could be recovered after washing the platelets. Frangulin B also selectively suppressed the thromboxane B2 formation caused by collagen, but not those by arachidonic acid and thrombin. Similarly, the formation of inositol phosphate caused by collagen was also suppressed by frangulin B, while that of PAF or thrombin was not affected. In the presence of PGE1, frangulin B also decreased Mg(2+)-dependent platelet adhesion to collagen. It is concluded that frangulin B may be an antagonist of collagen receptor in platelet membrane.