Therapeutic effect of Jagged1 DNA vaccine on collagen-induced arthritis

Abstract Notch signaling plays an important role in functional differentiation of mature T cells. Those findings have allowed us to examine whether modification of Notch signaling has therapeutic effects on immune-associated diseases. We here examined whether DNA vaccine of Jagged1, one of the Notch ligands, is able to prevent collagen-induced arthritis (CIA) in mice. The CIA was induced in male DBA/1J mice by immunizing bovine collagen type II. Those mice were vaccinated with extracellular region of Jagged1 (soluble form: sJagged1) gene three times every one week starting at 2 days before initial immunization. The mice vaccinated with sJagged1 showed reduced clinical score and disease incidence compared with control mice. Histological analysis also showed reduced infiltration of inflammatory cells in the joints by sJagged1-treated mice. The vaccination with sJagged1 did not affect the numbers of regulatory T cell and production of IL-10 from T cells. The coimmunization of OVA and full length Jagged1 reduced the number of OVA specific and granzyme B producing CD8+ T cells. These results indicate that Jagged1 suppresses antigen-specific CD8+ T cell functions resulted in reduced CIA score, suggesting that Jagged1 has the therapeutics effects on autoimmune diseases by suppressing T cell functions.