023 Lenabasum, a cannabinoid type 2 receptor agonist, exerts anti-inflammatory effects in dermatomyositis in Th1 cells

Dermatomyositis (DM) is a chronic, systemic autoimmune disease affecting the skin, muscle, and lungs. Lenabasum, non-psychoactive cannabinoid type 2 receptor (CB2R) agonist, currently being investigated as non-immunosuppressive treatment option for DM. The activation of CB2R has been shown to reduce several key pro-inflammatory cytokines implicated in Our lab previously demonstrated via immunohistochemistry (IHC) that Lenabasum decreases CD4, IFNβ, IFNγ IL31 expression DM skin at 12 weeks (p<0.05), with no differences IL4 compared placebo (p>0.05). In this study, we then utilized multiplexed flow cytometry leukocytes eluted from further analyze on cell lineages. When evaluating lineages, CD4 T helper (Th) subsets were gated CD4+ IFNγ+ Th1 CD4+IL4+ Th2. There was significantly higher frequency parent (FOP) percentage (p<0.05) (61.05%, n=6) versus Th2 cells (25.5%, n=6). Among myeloid there greater FOP M2 macrophages (CD68+CD163+), CD14++CD16++ macrophages, monocyte derived dendritic (moDCs; CD11c+CD14+). With 15mmol trend towards decrease of: TNFα macrophages; IFNβ Tcells; CD16+ cells; cells, CD14++CD16+ macrophages. also significant moDCs secreting (p<0.01). Imaging mass untreated highest MPI moDCs. elevated lesser extent other These data suggest may exert specific anti-inflammatory effects DM, particularly Th1-derived IL31.