콜레라 독소의 항원보조제 효과에서의 ERdj5의 역할에 관한 연구
- 주제(키워드) 콜레라독소 , ERdj5
- 발행기관 아주대학교
- 지도교수 장선영, 김수동
- 발행년도 2018
- 학위수여년월 2018. 8
- 학위명 석사
- 학과 및 전공 글로벌제약임상대학원 글로벌제약임상약학과
- 실제URI http://www.dcollection.net/handler/ajou/000000028181
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
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.
more목차
I. INTRODCUTION
II MATERIALS AND METHODS
A. Mice and immunization
B. Reagent
C.ELISA
D.Cell isolation
E.BMDC generation
F. Differentiation of OT-II T cells
G. Flow cytometry
H. Cytokines
I. Statistics
III. Results
A.ERdj5 is acritical factor for the production of Ag-specific AB following mucosal immunization
B. ERdj5 is independent of the cholera toxin of the B subunit for adjuvanticity
C. ERdj5 deficiency specifically reduced the production of Ag-specific IgG2c isotype
D. ERdj5 deficient dendritic cells impaired CT dependent activation
E. ERdj5 deficiency in DCs failed to induce pro-inflammatory cytokines following CT stimulation
F. ERdj5 deficiency reduced helper T cell generation
IV.Discussion
V. conclusion
References
국문요약
