title: Role of resveratrol-induced CD11b(+) Gr-1(+) myeloid derived suppressor cells (MDSCs) in the reduction of CXCR3(+) T cells and amelioration of chronic colitis in IL-10(-/-) mice.
abstract: Resveratrol, a naturally occurring polyphenol has received significant attention as a potent anti-inflammatory agent. Inflammatory bowel disease (IBD) is a chronic intestinal inflammation caused by hyperactivated effector immune cells that produce proinflammatory cytokines. Myeloid derived suppressor cells (MDSCs) are a heterogeneous population characterized by the co-expression of CD11b(+) and Gr-1(+) and have long been known for their immunosuppressive function. We report that resveratrol effectively attenuated overall clinical scores as well as various pathological markers of colitis in IL-10(-/-) mice by down regulating Th1 responses. Resveratrol lessened the colitis-associated decrease in body weight and increased levels of serum amyloid A (SAA), CXCL10 and colon TNF-α, IL-6, RANTES, IL-12 and IL-1β concentrations. After resveratrol treatment, the percentage of CXCR3 expressing T cells was decreased in the spleen, mesenteric lymph nodes (MLN), and intestinal lamina propria (LP). However, the percentage and absolute numbers of CD11b(+) and Gr-1(+)cells in the lamina propria (LP) and spleen were increased after resveratrol treatment as compared with the vehicle treatment. Co-culture of resveratrol-induced CD11b(+) Gr-1(+) cells with T cells, attenuated T cell proliferation, and most importantly reduced IFN-γ and GM-CSF production by LP derived T cells from vehicle treated IL-10(-/-) mice with chronic colitis. The current study suggests that administration of resveratrol into IL-10(-/-) mice induces immunosuppressive CD11b(+) Gr-1(+) MDSCs in the colon, which correlates with reversal of established chronic colitis, and down regulation of mucosal and systemic CXCR3(+) expressing effector T cells as well as inflammatory cytokines in the colon. The induction of immunosuppressive CD11b(+) Gr-1(+) cells by resveratrol during colitis is unique, and suggests an as-yet-unidentified mode of anti-inflammatory action of this plant polyphenol.
authors.affiliation: Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29208, USA.
authors.forename: Udai P
authors.initials: UP
authors.lastname: Singh
authors.forename: Narendra P
authors.initials: NP
authors.lastname: Singh
authors.forename: Balwan
authors.initials: B
authors.lastname: Singh
authors.forename: Lorne J
authors.initials: LJ
authors.lastname: Hofseth
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Taub
authors.forename: Robert L
authors.initials: RL
authors.lastname: Price
authors.forename: Mitzi
authors.initials: M
authors.lastname: Nagarkatti
authors.forename: Prakash S
authors.initials: PS
authors.lastname: Nagarkatti
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000502:physiology*; D049109:Cell Proliferation; D002469:Cell Separation; D002908:Chronic Disease; D003092:Colitis / Q000188:drug therapy* / Q000235:genetics*; D016207:Cytokines / Q000096:biosynthesis; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005243:Feces / Q000737:chemistry; D005434:Flow Cytometry; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009092:Mucous Membrane / Q000166:cytology; D022423:Myeloid Cells / Q000502:physiology*; D054367:Receptors, CXCR3 / Q000502:physiology*; D019707:Receptors, Chemokine / Q000502:physiology*; D000077185:Resveratrol; D000685:Serum Amyloid A Protein / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D013267:Stilbenes / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000502:physiology*; D015431:Weight Loss / Q000187:drug effects
chemical_list: D039481:CD11b Antigen; D016207:Cytokines; C503133:Gr-1 protein, mouse; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D000685:Serum Amyloid A Protein; D013267:Stilbenes; D016753:Interleukin-10; D000077185:Resveratrol