Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Article
  • Published:

TGF-β1 gene-modified, immature dendritic cells delay the development of inflammatory bowel disease by inducing CD4+Foxp3+ regulatory T cells

Cellular & Molecular Immunology volume 7, pages 35–43 (2010)Cite this article

A Correction to this article was published on 29 November 2019

Abstract

Inflammatory bowel disease (IBD) is caused by an uncontrolled immune response in the intestinal lumen, leading to inflammation in genetically predisposed individuals. Immunotherapy may be a promising approach to the treatment of IBD. Here, we show that transforming growth factor-β1 (TGF-β1) gene-modified immature dendritic cells (imDCs) could enhance the inhibitory function of imDCs and delay the progress of IBD induced by dextran sodium sulfate in mice. The results of fluorescence-activated cell sorter (FACS) demonstrated that this protective effect is mediated partially by inducing CD4+Foxp3+ regulatory T cells (Tregs) in mesentery lymph nodes to control inflammation. In vitro experiments also supported this hypothesis. In conclusion, we provide evidence that TGF-β1-modified bone marrow-derived imDCs may have a therapeutic effect to IBD.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  1. Papadakis KA, Targan SR . Role of cytokines in the pathogenesis of inflammatory bowel diseases. Annu Rev Med 2000; 51: 289–298.

    Article  CAS  Google Scholar 

  2. Loftus EV Jr . Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences. Gastroenterology 2004; 126: 1504–1517.

    Article  Google Scholar 

  3. Yu Y, Sitaraman S, Gewirtz AT . Intestinal epithelial cell regulation of mucosal inflammation. Immunol Res 2004; 29: 55–68.

    Article  CAS  Google Scholar 

  4. Kuhbacher T, Fölsch UR . Practical guidelines for the treatment of inflammatory bowel disease. World J Gastroenterol 2007; 13: 1149–1155.

    Article  CAS  Google Scholar 

  5. Pepper MS . Transforming growth factor-beta: vasculogenesis, angiogenesis and vessel wall integrity. Cytokine Growth Factor Rev 1997; 8: 21–43.

    Article  CAS  Google Scholar 

  6. Blobe GC, Schiemann WP, Lodish HF . Role of transforming growth factor beta in human disease. N Engl J Med 2000; 342: 1350–1358.

    Article  CAS  Google Scholar 

  7. Lawrance IC, Maxwell L, Doe W . Inflammation location, but not type, determines the increase in TGF-beta1 and IGF-1 expression and collagen deposition in IBD intestine. Inflamm Bowel Dis 2001; 7: 16–26.

    Article  CAS  Google Scholar 

  8. Banchereau J, Steinman RM . Dendritic cells and the control of immunity. Nature 1998; 192: 245–252.

    Article  Google Scholar 

  9. Steinman RM, Hawiger D, Nussenzweig MC . Tolerogenic dendritic cells. Annu Rev Immunol 2003; 21: 685–711.

    Article  CAS  Google Scholar 

  10. Wallet MA, Sen P, Tisch R . Immunoregulation of dendritic cells. Clin Med Res 2005; 3: 166–175.

    Article  CAS  Google Scholar 

  11. Zhang MH, Tang H, Guo ZH, An HZ, Zhu XJ, Song WG, et al. Splenic stroma drives mature dendritic cells to differentiate into regulatory dendritic cells. Nat Immunol 2004; 5: 1124–1133.

    Article  CAS  Google Scholar 

  12. Aharonia R, Sonegoa H, Brennerb O, Eilamb R, Arnon R . The therapeutic effect of glatiramer acetate in a murine model of inflammatory bowel disease is mediated by anti-inflammatory T-cells. J Pharmacol Exp Ther 2006; 318: 68–78.

    Article  Google Scholar 

  13. Sun WJ, Wang QX, Zhang LH, Pan JP, Zhang M, Lu GH, et al. TGF-β1 gene modified immature dendritic cells exhibit enhanced tolerogenicity but induce allograft fibrosis in vivo. J Mol Med 2002; 80: 514–523.

    Article  CAS  Google Scholar 

  14. Steinbrink K, Wolfl M, Jonuleit H, Knop J, Enk AH . Induction of tolerance by IL-10-treated dendritic cells. J Immunol 1997; 159: 4772–4780.

    CAS  Google Scholar 

  15. Trinchieri G . Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol 2003; 3: 133–146.

    Article  CAS  Google Scholar 

  16. Wing K, Fehervari Z, Sakaguchi S . Emerging possibilities in the development and function of regulatory T cells. Int Immunol 2006; 18: 991–1000.

    Article  CAS  Google Scholar 

  17. Podolsky DK . Inflammatory bowel disease. N Engl J Med 2002; 347: 417–429.

    Article  CAS  Google Scholar 

  18. Leehler R, Ng WF, Steinman RM . Dendritic cells in transplantation: friend or foe? Immunity 2001; 14: 357–368.

    Article  Google Scholar 

  19. Jong EC, Smits HH, Kapsenberg ML . Dendritic cell-mediated T cell polarization. Springer Semin Immunopathol 2005; 26: 289–307.

    Article  Google Scholar 

  20. Thomson AW, Lu L, Murase N, Demetris AJ, Rao AS, Starzl TE . Microchimerism, dendritic cell progenitors and transplantation tolerance. Stem Cells 1995; 13: 622–639.

    Article  CAS  Google Scholar 

  21. Placek K, Coffre M, Maiella S, Bianchi E, Rogge L . Genetic and epigenetic networks controlling T helper 1 cell differentiation. Immunology 2009; 127: 155–162.

    Article  CAS  Google Scholar 

  22. Cooper HS, Murthy SN, Shah RS, Sedergran DJ . Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest 1993; 69: 238–249.

    CAS  PubMed  Google Scholar 

  23. Sauer S, Bruno L, Hertweck A, Finlay D, Leleu M, Spivakov M, et al. T cell receptor signaling controls Foxp3 expression via PI3K, Akt, and mTOR. Proc Natl Acad Sci USA 2008; 105: 7797–7802.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Professor Lin-Rong Lu for his critical review of the manuscript. This work was supported by the National Key Basic Research Program of China (Grant 2007CB512400), the National High Technology Research and Development Program of China (Grants 2006AA02A239 and 2007AA021102), the National Natural Science Foundation of China (Grant 30671909 and 30972725) and Natural Science Foundation of Zhejiang Province (Z2090042).

Author information

Author notes

  1. Zhijian Cai and Wei Zhang: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China

    Zhijian Cai, Wei Zhang, Min Li, Yinpu Yue, Fei Yang, Lei Yu, Xuetao Cao & Jianli Wang

  2. Institute of Immunology and National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai, China

    Xuetao Cao

Authors
  1. Zhijian Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Min Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yinpu Yue
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fei Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lei Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xuetao Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jianli Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jianli Wang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cai, Z., Zhang, W., Li, M. et al. TGF-β1 gene-modified, immature dendritic cells delay the development of inflammatory bowel disease by inducing CD4+Foxp3+ regulatory T cells. Cell Mol Immunol 7, 35–43 (2010). https://doi.org/10.1038/cmi.2009.107

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/cmi.2009.107

Keywords

This article is cited by

Search

Advanced search

Quick links