155 VISTA regulates monocyte adhesion via TGF-beta; A targetable mechanism for hyper-adhesive monocytes in psoriasis?

V-domain Immunoglobulin Suppressor of T cell activation (VISTA) is an inhibitory B7 family immune-checkpoint molecule expressed on myeloid cells. VISTA-KO mice exhibit Psoriasis-like inflammation. Myeloid cells in psoriasis have multiple abnormalities, including aberrancies monocytic myeloid-derived suppressor and adhesiveness. Whether VISTA signaling related to Psoriasis dysfunction unknown. Indeed, monocytes contain a subset with dysregulated expression (MCF 347±32 psoriasis, n=10, vs MCF 462±77 controls , n=6), p< 0.05). To examine function monocytes, we generated lentivirus-induced overexpressing human (THP-1), stable THP-1 (THP-1VISTA) were established. Flow cytometric analysis showed that THP-1VISTA transfectants induced when activated by LPS alone or combination Interferon-γ. Morphologically, transfectants, but not GFP decreased aggregation. Next, interrogated the inflammatory cytokine profile observed using mRNA arrays. Relative GFP-transfectants, VISTA-overexpressing upregulated disintegrin-like metalloprotease domain thrombospondin type 1 motif (ADAMTS1), yet downregulated TGF-β, tissue inhibitor metalloproteinase (TIMP3), catenins (CTNNA1, CTNND1), matrix (MMP14), extracellular adhesion protein (ANOS1). Add-back experiments recombinant TGF-b restored aggregation, likely via its restoration integrin A6 (ITGA6) same level as control THP-1GFP. These findings uncover previously unappreciated connectivity between VISTA, TGF-b, monocyte adhesion, perhaps offering new intervention point relevant monocyte-mediated associated comorbidities.