Soluble CEACAM1 induces suppressive Tregs and binds to CD5 in a heterophilic manner

Introduction CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1) is an immune checkpoint regulator that controls immunity via self- and heteroligation. Soluble CEACAM1 (sCC1) was originally discovered as a serum marker in human patients with obstructive and autoimmune liver disease. In murine autoimmune hepatitis (Concanavalin A-induced hepatitis), CEACAM1 induces Tregs, and enhances Treg stability. Ceacam1-/- mice exhibit hyperinflammation and persistence of liver injury. IL-2-dependent Treg induction requires signaling via CEACAM1-S (CEACAM1 with a short cytoplasmic domain), on CD4+ T cells. Contrary, the long CEACAM1 isoform (CEACAM1-L) inhibits immune signaling via two ITIMs. It interacts with co-inhibitory immune receptors (e.g. TIM-3) and limits T cell activation. CD5 is a Treg marker that is implicated in Treg signaling and stability.