Cited by 92Inflammatory Bowel DiseaseImmune cells in cancerSirtuins and Resveratrol in Medicine

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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

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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.

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  • The Mediterranean diet has a well-established anti-inflammatory activity, mainly due to microbiota-derived short chain fatty acids induced by dietary fibre and high intake of omega-3 PUFA and antioxidants.

    “In addition to weight loss, the MD has been reported to have a well-established anti-inflammatory activity, which is mainly due to the microbiota-derived production of short chain fatty acids that are induced by dietary fibre [14] and the high intake of both polyunsaturated fatty acids (PUFA) omega 3 and antioxidants contained in fruits, vegetables, extra-virgin olive oil, and wine [15,16,17].”

    From Adherence to the Mediterranean Diet, Dietary Patterns and Body Composition in Women with Polycystic Ovary Syndrome (PCOS) (2019) · cites this paper as [17]

    The Introduction (page not provided) identifies resveratrol as a polyphenol found in grapes and red wine and describes its anti-inflammatory properties. The Results report reduced inflammatory cytokines after resveratrol treatment in mice with chronic colitis. The paper does not establish anti-inflammatory effects of the Mediterranean diet or attribute them to omega-3 intake, dietary fibre, or microbiota-derived short-chain fatty acids. (LLM, conf=0.86)

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Metadata

Authors
Singh, U. P., Singh, N. P., Singh, B., Hofseth, L. J., Taub, D. D., Price, R. L., Nagarkatti, M., & Nagarkatti, P. S.
Affiliations
  • University of South Carolina (US)
  • Emory University (US)
  • National Institutes of Health (US)
Corresponding author
Nagarkatti, Prakash S.
Venue
Brain, Behavior, and Immunity
Publisher
Elsevier BV
Published
2012-01
Volume
26
Issue
1
Pages
72-82
ISSN
0889-1591 (ISSN-L)
OpenAlex
W2069182180
Cited by
92
References
1
Citations by year
2025: 5 · 2024: 6 · 2023: 6 · 2022: 8 · 2021: 5 · 2020: 5 · 2019: 10 · 2018: 9 · 2017: 5 · 2016: 5 · 2015: 10 · 2014: 7 · 2013: 7 · 2012: 4
FWCI
3.59
Type
journal article
Language
en
Open access
Locations
  • Brain Behavior and Immunity (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of Mental Health (R01MH094755)
  • National Institute of Environmental Health Sciences (ES09098, R01ES009098, R01ES019313, ES019313)
  • National Center for Complementary and Integrative Health (P01AT003961)
Topics
  • Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
Keywords
resveratrol, myeloid-derived suppressor cells, CD11b+Gr1+ cells, chronic colitis, inflammatory bowel disease, IL-10 knockout mice, Th1 response, immunosuppression, anti-inflammatory polyphenols, lamina propria, interferon-gamma, GM-CSF, serum amyloid A, CXCL10, intestinal inflammation
MeSH terms
Resveratrol, Serum Amyloid A Protein, Animals, Cell Separation, Chronic Disease, Colitis, Enzyme-Linked Immunosorbent Assay, Feces, Flow Cytometry, Immunoglobulin A, Immunoglobulin G, Mucous Membrane, Spleen, Stilbenes, T-Lymphocytes, Weight Loss, Cytokines, Interleukin-10, Mice, Knockout, Disease Progression, Receptors, Chemokine, Myeloid Cells, CD11b Antigen, Cell Proliferation, Mice, Receptors, CXCR3

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