Cannabidiol alters macrophage differentiation resulting in accumulation of immunosuppressive myeloid cells and dendritic cells

Autor: Kathryn Miranda, Courtney Culpepper, Kiesha Wilson, Prakash S. Nagarkatti, Mitzi Nagarkatti
Rok vydání: 2020
Předmět:
Zdroj: The Journal of Immunology. 204:63.9-63.9
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.204.supp.63.9
Popis: Cannabidiol (CBD) is a non-psychoactive phytocannabinoid that has anti-inflammatory properties; however the precise immunological mechanisms involved are not clear. Research from our laboratory has established that CBD promotes expansion of immunosuppressive myeloid-derived suppressor cells (MDSC), which are immature leukocytes thought to have stalled their differentiation towards mature myeloid lineages such as macrophages and dendritic cells (DC). In the current study, we aimed to better understand the mechanisms of CBD-altered hematopoiesis. We performed flow cytometry and single cell RNA sequencing (sc-RNAseq) on peritoneal cells from C57BL/6 mice treated with Vehicle (Veh) or CBD (20mg/kg, i.p.). Consistent with our previous studies, CBD promoted accumulation of MDSCs after 24h, which dissipated after 48h. Strikingly, MDSC accumulation was preceded by ablation of macrophages, which was maintained beyond 48h. In addition, accumulation of DCs started at 12h and accelerated through 48h. Similarly, sc-RNAseq of peritoneal cells harvested at 24h showed two distinct populations of cells expressing Adgre1, which encodes F4/80. These two clusters were distinct between Veh- and CBD-treated mice due to their drastically altered transcriptomes. The Veh-distinct cluster was comprised of macrophages expressing complement genes, while the CBD-distinct cluster was comprised of MDSCs expressing Arg1. Furthermore, the DC cluster expressing Ccr2 was enlarged in CBD-treated mice. Together, our results demonstrate that CBD drastically alters hematopoiesis, depleting macrophages and promoting MDSCs and DCs. These findings suggest CBD treatment may be beneficial in various macrophage-driven inflammatory disorders.
Databáze: OpenAIRE
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