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

Brain Behav Immun. 2012 Jan;26(1):72-82. doi: 10.1016/j.bbi.2011.07.236. Epub 2011 Jul 23.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • CD11b Antigen / physiology*
  • Cell Proliferation
  • Cell Separation
  • Chronic Disease
  • Colitis / drug therapy*
  • Colitis / genetics*
  • Cytokines / biosynthesis
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Feces / chemistry
  • Flow Cytometry
  • Immunoglobulin A / biosynthesis
  • Immunoglobulin G / biosynthesis
  • Interleukin-10 / genetics
  • Interleukin-10 / physiology*
  • Mice
  • Mice, Knockout
  • Mucous Membrane / cytology
  • Myeloid Cells / physiology*
  • Receptors, CXCR3 / physiology*
  • Receptors, Chemokine / physiology*
  • Resveratrol
  • Serum Amyloid A Protein / metabolism
  • Spleen / cytology
  • Stilbenes / pharmacology*
  • T-Lymphocytes / physiology*
  • Weight Loss / drug effects


  • CD11b Antigen
  • Cytokines
  • Gr-1 protein, mouse
  • Immunoglobulin A
  • Immunoglobulin G
  • Receptors, CXCR3
  • Receptors, Chemokine
  • Serum Amyloid A Protein
  • Stilbenes
  • Interleukin-10
  • Resveratrol