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

First Author  Bartczak A Year  2017
Journal  World J Gastroenterol Volume  23
Issue  15 Pages  2673-2684
PubMed ID  28487604 Mgi Jnum  J:273734
Mgi Id  MGI:6282463 Doi  10.3748/wjg.v23.i15.2673
Citation  Bartczak A, et al. (2017) Overexpression of fibrinogen-like protein 2 protects against T cell-induced colitis. World J Gastroenterol 23(15):2673-2684
abstractText  AIM: To 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(-/-) 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.
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