Abstract
Intestinal disequilibrium leads to inflammatory bowel disease (IBD), and chronic inflammation predisposes to oncogenesis. Antigen-presenting dendritic cells (DCs) and macrophages can tip the equilibrium toward tolerance or pathology. Here we show that delta-9-tetrahydrocannabinol (THC) attenuates colitis-associated colon cancer and colitis induced by anti-CD40. Working through cannabinoid receptor 2 (CB2), THC increases CD103 expression on DCs and macrophages and upregulates TGF-β1 to increase T regulatory cells (Tregs). THC-induced Tregs are necessary to remedy systemic IFNγ and TNFα caused by anti-CD40, but CB2-mediated suppression of APCs by THC quenches pathogenic release of IL-22 and IL-17A in the colon. By examining tissues from multiple sites, we confirmed that THC affects DCs, especially in mucosal barrier sites in the colon and lungs, to reduce DC CD86. Using models of colitis and systemic inflammation we show that THC, through CB2, is a potent suppressor of aberrant immune responses by provoking coordination between APCs and Tregs.
Keywords: Cancer, Immunology
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of Interests The authors have declared that no conflicts of interest exist.
Similar articles
-
An endogenous aryl hydrocarbon receptor ligand, ITE, induces regulatory T cells and ameliorates experimental colitis.Am J Physiol Gastrointest Liver Physiol. 2018 Aug 1;315(2):G220-G230. doi: 10.1152/ajpgi.00413.2017. Epub 2018 Apr 19.PMID: 29672155 Free PMC article.
-
Δ9-tetrahydrocannabinol impairs the inflammatory response to influenza infection: role of antigen-presenting cells and the cannabinoid receptors 1 and 2.Toxicol Sci. 2013 Feb;131(2):419-33. doi: 10.1093/toxsci/kfs315. Epub 2012 Nov 14.PMID: 23152191 Free PMC article.
-
Suppression of CpG-ODN-mediated IFNα and TNFα response in human plasmacytoid dendritic cells (pDC) by cannabinoid receptor 2 (CB2)-specific agonists.Toxicol Appl Pharmacol. 2019 Apr 15;369:82-89. doi: 10.1016/j.taap.2019.02.013. Epub 2019 Feb 23.PMID: 30807757 Free PMC article.
-
Immunopathogenesis of Colitis-Associated Cancer in an Animal Model.Crit Rev Eukaryot Gene Expr. 2015;25(3):245-51. doi: 10.1615/critreveukaryotgeneexpr.2015013885.PMID: 26558947 Review.
-
IL-23 in inflammatory bowel diseases and colon cancer.Cytokine Growth Factor Rev. 2019 Feb;45:1-8. doi: 10.1016/j.cytogfr.2018.12.002. Epub 2018 Dec 12.PMID: 30563755 Review.
LinkOut – more resources
-
Miscellaneous