| First Author | Becker W | Year | 2020 |
| Journal | iScience | Volume | 23 |
| Issue | 9 | Pages | 101504 |
| PubMed ID | 32942172 | Mgi Jnum | J:306821 |
| Mgi Id | MGI:6717626 | Doi | 10.1016/j.isci.2020.101504 |
| Citation | Becker W, et al. (2020) Activation of Cannabinoid Receptor 2 Prevents Colitis-Associated Colon Cancer through Myeloid Cell De-activation Upstream of IL-22 Production. iScience 23(9):101504 |
| abstractText | 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-beta1 to increase T regulatory cells (Tregs). THC-induced Tregs are necessary to remedy systemic IFNgamma and TNFalpha 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. |
