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

Agata Bartczak, Jianhua Zhang, Oyedele Adeyi, Achiya Amir, David Grant, Reginald Gorczynski, Nazia Selzner, Andrzej Chruscinski, Gary A. Levy

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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 fgl2Tg 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, fgl2Tg Treg had enhanced immunosuppressive activity, and fgl2Tg 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. Fgl2Tg Treg prevented the development of T cell-induced colitis, whereas fgl2+/+ and fgl2-/- Treg were only partially protective. In mice that received fgl2Tg 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 fgl2Tg mice did not produce colitis. CONCLUSION: Here we show that fgl2Tg Teff are hypoproliferative and do not induce colitis. We further demonstrate that fgl2Tg 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.

Original languageEnglish (US)
Pages (from-to)2673-2684
Number of pages12
JournalWorld Journal of Gastroenterology
Volume23
Issue number15
DOIs
StatePublished - Apr 21 2017
Externally publishedYes

Bibliographical note

Funding Information:
Supported by the Heart and Stroke Foundation of Canada, No. G-13-0002851; the Canadian Institutes of Health Research Training Program in Regenerative Medicine to Bartczak A and Chruscinski A; and the Ontario Graduate Scholarship in Science and Technology to Bartczak A.

Keywords

  • Colitis
  • Fibrinogen-like protein 2
  • Inflammatory bowel disease
  • Regulatory T cells
  • Transgenic mouse

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