Cholera toxin (CT) is one of most strong mucosal adjuvant as well as enteric toxin. CT is composed of A-B molecules and B subunit binds to GM1 followed by entering host cells. The A subunit of CT is the molecule responsible for the toxic activity which has the enzymatic activity of ADP ribosylation and finally increase the concentration of cyclic AMP in the host cell, resulting in an abnormal water regulation in the intestinal epithelium or induction of proinflammatory cytokines in the innate immune cells. Erdj5 in the endoplasmic reticulum reduces disulfide bond of CT and enable to retro-translocation of CTA from endoplasmic reticulum to cytosol. In this study, we investigated physiological relevance of Erdj5 for immune stimulation by CT. Erdj5 knockout (KO) mice had decreased production of antigen specific IgG in the serum and IgA in the mucosal secretion after intra-nasal immunization of ovalbumin and CT. Especially, IgG2c isotype were specifically reduced in absence of Erdj5. Erdj5 KO DC failed to full activation with decreased expression of costimulatory molecules such as MHC class II, CD80, and CD 86. In addition, Erdj5 KO DC secreted reduced proinflammatory cytokines such as TNF-and IL-6. Cytokine signature of Th17 and Th2 were reduced in the cervical lymph node of Erdj5 KO mice following intranasal immunization. These result suggested that Erdj5 contributes to a decisive factor in the immunostimulatory capacity of CT.