An anti-inflammatory gene expression signature is associated with CBD treatment in people living with HIV

Simone Marini
University of Florida

Co-Authors: Amanda Huber¹, Melanie N. Cash², Marco Salemi², Robert L. Cook², Paul Borsa², Carla Mavian^2
1University of Michigan ²University of Florida

Introduction
HIV-related comorbidities appear to be related to chronic inflammation, a condition characterizing people living with HIV (PLWH). Prior work indicates that cannabidiol (CBD) might reduce inflammation; however, the genetics underpinning this effect are not well investigated. In this work, we detect gene expression changes in human peripheral blood mononuclear cells (PBMCs) from PLWH after at least one month of CBD treatment.

Methods
We collected PBMCs three HIV-positive subjects at baseline and after CBD treatment (at least 27 days) via single-cell RNA sequencing. After quality control, we obtained a data set of ~30,300 cells expressing a total of ~42,000 distinct genes.

Results
We identified of seven cell populations: CD4 T cells, CD8 T cells, NKT cells, NK cells, Myeloid cells (including monocytes), B cells and plasmablasts/plasma cells. Gene expression analysis revealed myeloid cells to carry a CBD-associated anti-inflammatory signature. The signatures including genes such CXCL8, CCL3, EREG, IL1B, KLF6, JUN and FOS, all underexpressed after CBD treatment. To further confirm the anti-inflammatory shift in myeloid cells, we designed an inflammation score based on a group of over 100 genes under the Gene Ontology term \”\”Positive regulation of inflammatory response\”\”. The score decreases 12% after CBD in myeloid cells, and the decrease is conserved by analyzing the score distribution per subject. Decline in c-reactive protein (CRP) and erythrocyte sedimentation rate was also observed.

Conclusions
Our study shows how CBD is associated with underexpression of pro-inflammatory genes in myeloid cells after CBD treatment. While this study helps understand the genetic underpinning of CBD anti-inflammatory action, and the potential of its anti-inflammatory effects, the molecular chain leading to inflammation reduction remains to be unveiled.