IBD
Under normal physiological conditions, gut homeostasis is maintained by different innate immune cells that stimulate or suppress T cell differentiation and activation. While the exact cause of Inflammatory bowel disease (IBD) is still not fully understood, research suggests an improper and overreactive immune response drives the chronic inflammation. Key immune cells involved are gut resident T helper 17 (Th17) cells, a subset of T helper cells, which orchestrate the mucosal defense against pathogens. Immune cells express various types of receptors that play crucial roles in recognizing and responding to different signals. Among these receptors included also different endocannabinoid receptors. Particularly, Th17 cells were shown to express different endocannabinoid receptors. Therefore, we are currently investigating whether plant-derived cannabinoids can modulate Th17 activity through their interaction with this system. To that end, we are utilizing a dextran sodium sulfate (DSS)-induced colitis in-vivo model that affords deeper understanding into the inflammatory processes and tissue damage associated with IBD. We are also employing this model to explore the effects of different tryptamines from various mushroom species of psilocybe.
CXCR4
C-X-C chemokine receptor type 4 (CXCR4) is a G protein-coupled receptor that serves as the cognate receptor for the α-chemokine C-X-C motif chemokine ligand 12 (CXCL12). This receptor is expressed on various cell types and plays pivotal roles in immune cell trafficking. Elevated levels of CXCR4 and CXCL12 have been implicated in the progression of several inflammatory conditions, such as rheumatoid arthritis, chronic liver inflammation, and inflammatory bowel disease. As some studies demonstrated that cannabinoids can modulate the expression and secretion of cytokines, we set out to examine whether they can modulate the chemokine-mediated infiltration of leukocytes into inflamed tissue through the CXCL12/CXCR4 axis. We have discovered a specific combination of two cannabinoids that effectively reduces CXCR4 expression; we are currently investigating the underlying molecular mechanism.
MDSCs
The generation and expansion of regulatory myeloid cells are one of the main mechanisms adopted by cancer cells to ensure tumor progression and metastasis formation. Key players are myeloid-derived suppressor cells (MDSCs), a heterogeneous group of immune cells derived from myeloid progenitor cells in the bone marrow. They are renowned for their immunosuppressive properties and play a pivotal role in regulating the immune response in various pathological conditions, including cancer, inflammation, and autoimmune diseases. Once activated, MDSCs express various immunosuppressive markers, such as inducible nitric oxide synthase (iNOS) and Arginase-1 (Arg-1), leading to diminished CD8+ T-cell proliferation and activation. As immune cells express different endocannabinoid receptors, our current focus lies in investigating the direct effect of cannabinoids on MDSC modulation. This research endeavor seeks to gain deeper insights into enhancing immunotherapy with cannabinoids.