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Peristaltic movement of the intestine propels food down the length of the gastrointestinal tract to promote nutrient absorption. Interactions between intestinal macrophages and the enteric nervous system regulate gastrointestinal motility, yet we have an incomplete understanding of the molecular mediators of this crosstalk. Here, we identify complement component 1q (C1q) as a macrophage product that regulates gut motility. Macrophages were the predominant source of C1q in the mouse intestine and most extraintestinal tissues. Although C1q mediates the complement-mediated killing of bacteria in the bloodstream, we found that C1q was not essential for the immune defense of the intestine. Instead, C1q-expressing macrophages were located in the intestinal submucosal and myenteric plexuses where they were closely associated with enteric neurons and expressed surface markers characteristic of nerve-adjacent macrophages in other tissues. Mice with a macrophage-specific deletion of C1qa showed changes in enteric neuronal gene expression, increased neurogenic activity of peristalsis, and accelerated intestinal transit. Our findings identify C1q as a key regulator of gastrointestinal motility and provide enhanced insight into the crosstalk between macrophages and the enteric nervous system.

Cannabinoid-based therapies are increasingly being used by cancer patients to treat chemotherapy-induced nausea and vomiting. Recently, cannabinoids have gained increased attention for their effects on cancer growth. Indeed, the effect of CB2 (JWH-015, JWH-133) agonists on breast cancer models have shown to reduce the size of breast cancer tumors. However, these studies assessing breast cancer progression were using CB2 agonist administered early into the cancer progression therefore assessing their effects on already established tumors is a critical need. In our study, we evaluate tumor growth using an ectopic xenograft ovarian (SKOV-3 and OVCAR-5) cancer model. The impact of chronic (30 days) administration of CB2 (JWH-133) agonist will be evaluated and started on 30 days of ectopic ovarian tumors. We will then evaluate and determine the mechanisms involved in ovarian cancer tumor growth by measuring levels of anandamide and 2-arachidonoyl glycerol as well as protein levels of CB1, CB2, ERα, ERβ, GPER, TNFα, IL-1β and IL-6 in ovarian and tumor tissues. Our results demonstrate a significant increase in ectopic ovarian tumor growth following chronic administration of JWH-133. Ovarian cancer tumor tissues chronically (30 days) treated with JWH-133 in comparison to vehicle treated groups showed an increase in endocannabinoid (AEA and 2-AG) and protein (CB2 and TNFα) levels with a decrease in GPER protein levels. Interestingly, our study emphasizes the importance of studying the impact of cannabinoid compounds on already established tumors to improve our understanding of cannabinoid-based therapies and, therefore better address clinical needs in cancer patients.