Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Apr;136(4):1308-16, e1-3.
doi: 10.1053/j.gastro.2008.12.053. Epub 2008 Dec 27.

Smad7 controls resistance of colitogenic T cells to regulatory T cell-mediated suppression

Massimo C Fantini  1 , Angelamaria Rizzo, Daniele Fina, Roberta Caruso, Massimiliano Sarra, Carmine Stolfi, Christoph Becker, Thomas T Macdonald, Francesco Pallone, Markus F Neurath, Giovanni Monteleone
Affiliations

Smad7 controls resistance of colitogenic T cells to regulatory T cell-mediated suppression

Massimo C Fantini et al. Gastroenterology. 2009 Apr.

Abstract

Background & aims: Foxp3-expressing regulatory T cells (Tregs) play a key role in the maintenance of the gut immune homeostasis, and an intact transforming growth factor (TGF)-beta signaling is required for their function. In inflammatory bowel disease (IBD), the TGF-beta signaling is impaired because of high expression of the inhibitory molecule Smad7. Although no intrinsic defects in Tregs function have been shown in IBD, it is still unknown whether colitogenic T cells are susceptible to Treg-mediated suppression. In this study, we have investigated whether IBD mucosal CD4+ T cells are resistant to Tregs and whether Smad7 is involved in this process.

Methods: IBD lamina propria mononuclear cells (LPMC) were cultured with or without Tregs, and proliferation was assessed by flow cytometry. Proliferation of IBD LPMC was also evaluated after Smad7 antisense oligonuclotide treatment. Treg-mediated suppression of T-cell proliferation and proinflammatory cytokine expression was investigated in murine Smad7 transgenic cells. In vivo, the Smad7-dependent resistance of colitogenic naïve T cells to Tregs was studied in the adoptive transfer model of colitis.

Results: IBD LPMC were resistant to Treg-mediated suppression, and this phenomenon was reverted by Smad7 antisense treatment. Consistently, CD4+ T cells isolated from Smad7 transgenic mice showed high proliferation, produced considerable amount of inflammatory cytokines following activation, and induced a severe colitis when transferred in immunodeficient RAG1 knockout mice even in the presence of wild-type Tregs.

Conclusions: Smad7 makes CD4+ T cells resistant to Tregs-mediated suppression thus fine-tuning their proinflammatory potential.

PubMed Disclaimer

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources