Improved Immune Suppressive Activity of Induced Regulatory T cells Expressing C/EBPβ in Inflammatory Bowel Disease

regulatory T cell;C/EBPβ;inflammatory bowel disease;interleukin-10;Dextran Sulfate Sodium;570

Ye eun Joo자연과학대학 생명과학부 ;

University:서울대학교 대학원

关键词: regulatory T cell;    C/EBPβ;    inflammatory bowel disease;    interleukin-10;    Dextran Sulfate Sodium;    570;   

Others  :  http://s-space.snu.ac.kr/bitstream/10371/138072/1/000000145066.pdf

美国|英语

来源: Seoul National University Open Repository

【 摘 要 】

The prevalence of the inflammatory bowel disease(IBD) is increasing worldwide, not to mention in the Western countries but also in Eastern Asia countries considered low risk in the past. The absolute cure for the IBD, however, is not achieved with the current treatments. Notwithstanding the exact cause of IBD is still under investigated, inflammatory nature of IBD is generally accepted idea. A new therapy using regulatory T(Treg) cell is considered as a promising candidate because Treg cells have capacity for both down-regulating specific pro-inflammatory target cells and repairing the tissue damage. It’s previously been reported that the stability of C/EBPβ overexpressed in vitro cultured TGFβ induced Treg cells(C/EBPβ_iTreg cells) is enhanced when most of its counterpart control TGFβ induced Treg cells(NGFR_iTreg cells) cultured in the same way turn into pathogenic ex-iTreg cells under acute inflammatory environments. Therefore, in this study, the stability and anti-inflammatory function of C/EBPβ_iTreg cells were examined in physiological context under severe inflammatory condition employing Dextran Sulphate Sodium(DSS) induced colitis mouse model. A certain degree of the inflammation caused by DSS was being rescued by intraperitoneal injection of C/EBPβ_iTreg cells comparing to control iTreg cells injection. The degree of inflammation was evaluated by the ration of he body weight change, colon length, and histological analysis. Additionally, Type1 T helper related cytokines’ mRNA levels(IFNΥ, TNFα and IL-12) in the distal colon of the mice with DSS are reduced by injecting C/EBPβ_iTreg cells. In order to find the cause of its improved anti-inflammatory function, the mRNA level of the well-known suppressive cytokines(IL-10, CTLA-4 and TGFβ) were measured. IL-10 mRNA level, among others, was increased in vitro cultured C/EBPβ_iTreg cells comparing to the control iTreg cells. All told, IL-10 might be a major player in remitting the colitis. The mechanism how C/EBPβoverexpression in iTreg cells increases IL-10 production is in question and its association with enhanced iTreg cell’s stability needs to be investigated further.