A single-nucleus multiome analysis of transcriptome and chromatin accessibility reveals cell-type-specific immune modulation for chronic cannabis use among people with HIV infection
Year: 2026
Type: preprint
Study design: Observational Study
Abstract: As cannabis use continues to rise among people with HIV (PWH), understanding its impact on immune function in this population is becoming increasingly important. To provide new insights on how cannabis modulates immune function, we analyzed single-nucleus multi-omic profiles of peripheral blood mononuclear cells (PBMCs) from PWH to characterize the changes in gene expression and chromatin accessibility associated with chronic cannabis exposure. We identified numerous differentially expressed genes (DEGs) between cannabis users and non-users in each cell type, approximately half of which were unique to individual cell types. Changes in pro- and anti-inflammatory gene expression associated with cannabis use are dependent on cell lineage and type. We identified hundreds of differential chromatin accessibility regions in each cell type, including cis -regulatory elements correlated with cell-type-dependent DEGs (e.g. NFKBIA in CD4+ T cells and CCL3L1 in classical monocytes). Multiple cannabis-associated transcription factors (e.g., NFKB1, FOS , and TCF7 ) emerge as regulators of the differentially expressed inflammatory genes. Furthermore, cannabis altered the communication between classical monocytes and lymphocytes. These findings indicate that cannabis-induced immunomodulatory effects are profound, dynamic and complex among cell types and that transcriptional changes are regulated at least in part by epigenetic mechanisms.
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Translational Biomedical Science Training Grant, Using Omics to Understand the Effects of Drug Abuse on HIV Latent Reservoir, Georgetown-Howard Universities Center for Clinical and Translational Science (GHUCCTS), Feature selection of DNA methylation biosignatures for neuropathy with comorbid drug abuse in the setting of HIV infection, Defining the impact of injection drug use on antiretroviral therapy and HIV treatment outcomes: an (epi)genomic approach, Gene Network Identification and Integration (GNetii) Approach to Understanding the Biology Underlying HIV and Drug Abuse., Clinical and Translational Science Institute, University of Miami Developmental HIV/AIDS Mental Health Research Center (D-ARC), Using Omics to Understand the Effects of Drug Abuse on HIV Latent Reservoir, Institutional Career Development Core, Johns Hopkins Institute for Clinical and Translational Research, University of Pittsburgh MACS/WIHS CCS, MACS/WIHS -CCS, In vivo study of THC-induced immunogenome changes at single cell resolution in HIV-infected humans, SF Bay Area MACS/WIHS Combined Cohort Study, UNC MACS/WIHS Combined Cohort Study Clinical Research Site, Surviving the HIV Epidemic (S/HE) in metropolitan Washington DC - Advancing knowledge through cohort studies, Center for AIDS Research at Emory University, Stress-immune mechanisms for people living with HIV, CUD and Depression, Northwestern CORE Clinical Research Site: Trans-omics for HIV/AIDS Research, Los Angeles CRS for the MACS/WIHS Combined Cohort Study, Data Analysis and Coordination Center for the MACS-WIHS Combined Cohort Study, Cell-type based epigenomic analysis to identify druggable genes for people living with HIV infection and using cannabis, MACS/WIHS Combined Cohort Study: Cook County Clinical Research Site (CC_CRS), The University of North Carolina Center for AIDS Research, MACS/WIHS Combined Cohort Study: Brooklyn Clinical Research Site (Bklyn CRS), Clinical Research Sites for the MACS/WIHS Combined Cohort Study (MACS/WIHS-CCS) - Baltimore/Wash DC Center, Atlanta MACS/WIHS Combined Cohort Study Clinical Research Site, UAB-MISS MACS/WIHS Combined Cohort Study, Miami Center for AIDS Research, UCLA Clinical and Translational Science Institute, Clinical Research Sites for the MACS/WIHS Combined Cohort Study (MACS/WIHS-CCS), UAB Center for AIDS Research (CFAR)
OpenAlex ID: W7131874303