ABSTRACT
Inflammatory bowel diseases (IBDs) are chronic intestinal disorders often characterized by a dysregulation of T cells, specifically T helper (Th) 1, 17 and T regulatory (Treg) repertoire. Increasing evidence demonstrates that dietary polyphenols from Mangifera indica L. extract (MIE, commonly known as mango) mitigate intestinal inflammation and splenic Th17/Treg ratio. In this study, we aimed to dissect the immunomodulatory and anti-inflammatory properties of MIE using a reverse translational approach, by initially using blood from an adult IBD inception cohort and then investigating the mechanism of action in a preclinical model of T cell-driven colitis. Of clinical relevance, MIE modulates TNF-α and IL-17 levels in LPS spiked sera from IBD patients as an ex vivo model of intestinal barrier breakdown. Preclinically, therapeutic administration of MIE significantly reduced colitis severity, pathogenic T-cell intestinal infiltrate and intestinal pro-inflammatory mediators (IL-6, IL-17A, TNF-α, IL-2, IL-22). Moreover, MIE reversed colitis-induced gut permeability and restored tight junction functionality and intestinal metabolites. Mechanistic insights revealed MIE had direct effects on blood vascular endothelial cells, blocking TNF-α/IFN-γ-induced up-regulation of COX-2 and the DP2 receptors. Collectively, we demonstrate the therapeutic potential of MIE to reverse the immunological perturbance during the onset of colitis and dampen the systemic inflammatory response, paving the way for its clinical use as nutraceutical and/or functional food.
Subject(s)
Colitis , Inflammatory Bowel Diseases , Mangifera , Adult , Humans , Animals , Tumor Necrosis Factor-alpha/metabolism , Endothelial Cells/metabolism , Intestinal Mucosa , Disease Models, AnimalABSTRACT
Rheumatoid arthritis is an immune-mediated inflammatory disease of the synovium. Yet we still lack robust tissue-specific (synovial) biomarkers that are able to guide clinical decisions and stratify patients according to their disease subgroup and predicted response to treatment. The EULAR Synovitis Study Group and the OMERACT synovial tissue biopsy (STB) Special Interests Group have undertaken a consensus exercise to identify factors that are important for the standardisation of STB handling and analytical procedures in two situations-clinical practice and translational research.