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Overexpression of fibrinogen-like protein 2 protects against T cell-induced colitis

World Journal of Gastroenterology 2017年第15期23卷 2673-2684页

作者： Agata Bartczak Jianhua Zhang Oyedele Adeyi Achiya Amir David Grant Reginald Gorczynski Nazia Selzner Andrzej Chruscinski Gary A Levy Multi Organ Transplant Program University Health Network Department of Laboratory Medicine and Pathology University Health Network Gastroenterology Hepatology and Nutrition DivisionThe Hospital for Sick Children

AIM To determine the effect of overexpression of fibrinogenlike protein 2(FGL2) on regulatory T cell(Treg) and effector T(Teff) cell function on T cell-induced colitis in Rag1-/-mice.METHODS Treg and Teff cells from fgl2-/-, fgl2+/+, and fgl2 Tg mice were purified by FACS. They were studied in vitro for immunosuppressive activity and cell proliferation and in vivo for their effects on the development and prevention of T cell-induced colitis in Rag1-/-mice. RESULTS In vitro, fgl2 Tg Treg had enhanced immunosuppressive activity, and fgl2 Tg Teff had reduced proliferation to alloantigen stimulation. Transfer of Teff from C57Bl/6J mice(fgl2+/+) into Rag1-/-mice produced both clinical and histologic colitis with dense infiltrates of CD3+ T cells, crypt abscesses and loss of goblet cells. Fgl2 Tg Treg prevented the development of T cell-induced colitis, whereas fgl2+/+ and fgl2-/-Treg were only partially protective. In mice that received fgl2 Tg Treg, the ratio of Foxp3+ to CD3+ cells was increased both in the colon and in mesenteric lymph nodes, and Teff cell proliferation as determined by staining with Ki67 was reduced. Teff cells from fgl2 Tg mice did not produce colitis. CONCLUSION Here we show that fgl2 Tg Teff are hypoproliferative and do not induce colitis. We further demonstrate that fgl2 Tg Treg prevent colitis in contrast to fgl2+/+ Treg, which were only partially protective. These studies collectively provide a rationale for exploring the use of FGL2 or Treg expressing high levels of FGL2 in the treatment of inflammatory bowel disease.

关键词：像纤维蛋白原的蛋白质 2 大肠炎规章的 T 房间转基因的老鼠煽动性的肠疾病

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