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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
Open accessAbstract
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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Barrea, L., Arnone, A., Annunziata, G., Muscogiuri, G., Laudisio, D., Salzano, C., Pugliese, G., Colao, A., & Savastano, S. (2019) · Nutrients · doi:10.3390/nu11102278 · Cited by 306
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)
- PMC
- PMC3506001
- 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
- green
- europepmc.org
- 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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