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

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.