AIMTo determine the effect of overexpression of fibrinogen-like protein 2(FGL2)on regulatory T cell(Treg)and effector T(Teff)cell function on T cell-induced colitis in Rag1<sup>-/-</sup>mice.METHODSTreg an...AIMTo determine the effect of overexpression of fibrinogen-like protein 2(FGL2)on regulatory T cell(Treg)and effector T(Teff)cell function on T cell-induced colitis in Rag1<sup>-/-</sup>mice.METHODSTreg and Teff cells from fgl2<sup>-/-</sup>,fgl2<sup>+/+</sup>,and fgl2<sup>Tg</sup>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<sup>-/-</sup>mice.RESULTSIn vitro,fgl2<sup>Tg</sup>Treg had enhanced immunosuppressive activity,and fgl2<sup>Tg</sup>Teff had reduced proliferation to alloantigen stimulation.Transfer of Teff from C57Bl/6J mice(fgl2<sup>+/+</sup>)into Rag1<sup>-/-</sup>mice produced both clinical and histologic colitis with dense infiltrates of CD3<sup>+</sup>T cells,crypt abscesses and loss of goblet cells.Fgl2<sup>Tg</sup>Treg prevented the development of T cell-induced colitis,whereas fgl2<sup>+/+</sup>and fgl2<sup>-/-</sup>Treg were only partially protective.In mice that received fgl2<sup>Tg</sup>Treg,the ratio of Foxp3<sup>+</sup>to CD3<sup>+</sup>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<sup>Tg</sup>mice did not produce colitis.CONCLUSIONHere we show that fgl2<sup>Tg</sup>Teff are hypoproliferative and do not induce colitis.We further demonstrate that fgl2<sup>Tg</sup>Treg prevent colitis in contrast to fgl2<sup>+/+</sup>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.展开更多
基金Supported by the Heart and Stroke Foundation of Canada,No.G-13-0002851the Canadian Institutes of Health Research Training Program in Regenerative Medicine to Bartczak A and Chruscinski Athe Ontario Graduate Scholarship in Science and Technology to Bartczak A.
文摘AIMTo determine the effect of overexpression of fibrinogen-like protein 2(FGL2)on regulatory T cell(Treg)and effector T(Teff)cell function on T cell-induced colitis in Rag1<sup>-/-</sup>mice.METHODSTreg and Teff cells from fgl2<sup>-/-</sup>,fgl2<sup>+/+</sup>,and fgl2<sup>Tg</sup>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<sup>-/-</sup>mice.RESULTSIn vitro,fgl2<sup>Tg</sup>Treg had enhanced immunosuppressive activity,and fgl2<sup>Tg</sup>Teff had reduced proliferation to alloantigen stimulation.Transfer of Teff from C57Bl/6J mice(fgl2<sup>+/+</sup>)into Rag1<sup>-/-</sup>mice produced both clinical and histologic colitis with dense infiltrates of CD3<sup>+</sup>T cells,crypt abscesses and loss of goblet cells.Fgl2<sup>Tg</sup>Treg prevented the development of T cell-induced colitis,whereas fgl2<sup>+/+</sup>and fgl2<sup>-/-</sup>Treg were only partially protective.In mice that received fgl2<sup>Tg</sup>Treg,the ratio of Foxp3<sup>+</sup>to CD3<sup>+</sup>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<sup>Tg</sup>mice did not produce colitis.CONCLUSIONHere we show that fgl2<sup>Tg</sup>Teff are hypoproliferative and do not induce colitis.We further demonstrate that fgl2<sup>Tg</sup>Treg prevent colitis in contrast to fgl2<sup>+/+</sup>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.
