title: Apple polyphenols require T cells to ameliorate dextran sulfate sodium-induced colitis and dampen proinflammatory cytokine expression.
abstract: Human IBD, including UC and Crohn's disease, is characterized by a chronic, relapsing, and remitting condition that exhibits various features of immunological inflammation and affects at least one/1000 people in Western countries. Polyphenol extracts from a variety of plants have been shown to have immunomodulatory and anti-inflammatory effects. In this study, treatment with APP was investigated to ameliorate chemically induced colitis. Oral but not peritoneal administration of APP during colitis induction significantly protected C57BL/6 mice against disease, as evidenced by the lack of weight loss, colonic inflammation, and shortening of the colon. APP administration dampened the mRNA expression of IL-1β, TNF-α, IL-6, IL-17, IL-22, CXCL9, CXCL10, CXCL11, and IFN-γ in the colons of mice with colitis. APP-mediated protection requires T cells, as protection was abated in Rag-1(-/-) or TCRα(-/-) mice but not in IL-10(-/-), IRF-1(-/-), μMT, or TCRδ(-/-) mice. Administration of APP during colitis to TCRα(-/-) mice actually enhanced proinflammatory cytokine expression, further demonstrating a requirement for TCRαβ cells in APP-mediated protection. APP treatment also inhibited CXCR3 expression by TCRαβ cells, but not B or NK cells, in the colons of mice with colitis; however, depletion of CD4(+) or CD8(+) T cells alone did not abolish APP-mediated protection. Collectively, these results show that oral administration of APP protects against experimental colitis and diminishes proinflammatory cytokine expression via T cells.
authors.affiliation: Department of Immunology and Infectious Diseases, Montana State University, Bozeman, Montana, USA.
authors.forename: Jerod A
authors.initials: JA
authors.lastname: Skyberg
authors.forename: Amy
authors.initials: A
authors.lastname: Robison
authors.forename: Sarah
authors.initials: S
authors.lastname: Golden
authors.forename: Maryclare F
authors.initials: MF
authors.lastname: Rollins
authors.forename: Gayle
authors.initials: G
authors.lastname: Callis
authors.forename: Eduardo
authors.initials: E
authors.lastname: Huarte
authors.forename: Irina
authors.initials: I
authors.lastname: Kochetkova
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jutila
authors.forename: David W
authors.initials: DW
authors.lastname: Pascual
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D016264:Dextran Sulfate / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D008297:Male; D027845:Malus / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D059808:Polyphenols / Q000737:chemistry / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000473:pathology*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D059808:Polyphenols; D016264:Dextran Sulfate