IL-1beta secreted by CD11b+Gr-1+ myeloid cells derive autoimmunity during persistent Salmonella exposure in a MyD88-independent manner
- 주제(키워드) IL-1 beta , MyD88 , Salmonella
- 발행기관 고려대학교 대학원
- 지도교수 박세호
- 발행년도 2010
- 학위수여년월 2010. 2
- 학위구분 석사
- 학과 일반대학원 생명공학과
- 세부전공 세포생물학전공
- 원문페이지 51 p
- 비고 국제백신연구소 (권미나)
- 실제URI http://www.dcollection.net/handler/korea/000000021021
- 본문언어 영어
- 제출원본 000045589042
초록/요약
Oral administration of recombinant attenuated Salmonella Typhimurium vaccine (RASV) strain in MyD88-/- mice resulted in hypergammaglobulinemia accompanying splenomegaly and lymphadenopathy. Further, anti-dsDNA Ab in sera and the deposition of immune-complex in the kidney were detected in RASV-administered MyD88-/- mice, suggesting onset of autoimmunity. The depletion of CD4+ T cells completely blocked the hypergammaglobulinemia in RASV-administered-MyD88-/- mice. The expression of ICOS, PD-1, IL-21, and CXCR5 on CD4+ T cells were dramatically increased in RASV-administered MyD88-/- mice, suggesting that they have similar features with T follicular helper (Tfh) cells. Of note, CD11b+Gr-1+ myeloid cells expressing MHC Class II, CD40, CD80, CD86, PD-L1 and ICOS-L were also drastically expanded in the spleen of MyD88-/- mice after oral RASV challenge. They produced high levels of IL-1beta and IL-6 against Salmonella restimulation in vitro, and existed adjacent to CD4+ T cells in the extrafollicular region of the spleen. Furthermore, blockade of ICOS and IL-1beta inhibited the generation of hypergammaglobulinemia in RASV-administered MyD88-/- mice. Overall, these results suggest that generation of Tfh cells by IL-1beta-secreting CD11b+Gr-1+ cells in MyD88-/- mice with chronic Salmonella infection triggered autoimmune hypergammaglobulinemia by the ICOS-dependent and MyD88-independent manner.
more목차
1.Abstract 1
2.Introduction 2
3.Materials and Methods 5
4.Result
4.1RASV-administered MyD88-/- mice showed hypergammagloblinemia and autoimmunity 10
4.2Oral administration of MyD88-/- mice with RASV resulted in splenomegaly with chronic infection 13
4.3CD4+ T cells is indispensible for the generation of B cell responses in MyD88-/- mice after RASV challenge 18
4.4CD11b+Gr-1+ myeloid cells expanded in MyD88-/- mice after oral RASV challenge provide a milieu for B cells hyperactivation by secretion of IL-1 beta and IL-6 22
4.5The expanded CD11b+Gr-1+ myeloid cells meet CD4+ T cells in extrafollicular site of spleen and drive the CD4+ T cells activation 27
4.6Blockade of IL-1beta signaling inhibit the generation of hypergammaglobulinemia in RASV-administered MyD88-/- mice 33
5.Discussion 36
6.References 40
7.Abstract in Korean 44
8.Acknowledgment 45
