Soluble CEACAM1 induces activation of STAT5, Foxp3 expression and proliferation of Tregs in DC- T cell cocultures

CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1) is a homophilic and heterophilic adhesion molecule that acts as an immune co-receptor on leukocytes. Soluble CEACAM1 (sCC1) was originally discovered as a serum marker in human patients with cholestasis and autoimmune liver disease. In murine immune-mediated hepatitis (Concanavalin A-induced hepatitis), CEACAM1 promotes IL-2-dependent Treg induction and stability, and Ceacam1 -/- mice exhibit hyperinflammation and persistence of liver injury. This immune-regulatory function requires tight regulation of CEACAM1 isoform expression; on CD4+ T cells, CEACAM1-S, the activatory isoform with a short cytoplasmic domain, fosters cytokine production and Treg induction. Contrary, its inhibitory isoform with two ITIMs and a long cytoplasmic tail (CEACAM1-L) interacts with co-inhibitory immune receptors (e.g. TIM-3) and limits activation.