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Blocking Smad7 restores TGF-β1 signaling in chronic inflammatory bowel disease
Open accessAbstract
TGF-beta1 functions as a negative regulator of T cell immune responses, signaling to target cells using the Smad family of proteins. We show here that Smad7, an inhibitor of TGF-beta1 signaling, is overexpressed in inflammatory bowel disease (IBD) mucosa and purified mucosal T cells. Both whole tissue and isolated cells exhibit defective signaling through this pathway, as measured by phospho-Smad3 immunoreactivity. Specific antisense oligonucleotides for Smad7 reduce Smad7 protein expression in cells isolated from patients with IBD, permitting the cells to respond to exogenous TGF-beta1. TGF-beta1 cannot inhibit proinflammatory cytokine production in isolated lamina propria mononuclear cells from patients with Crohn disease (CD), but inhibition of Smad7 restores TGF-beta1 signaling and enables TGF-beta1 to inhibit cytokine production. In inflamed mucosal tissue explants from patients with CD, inhibition of Smad7 also restores p-Smad3 and decreases proinflammatory cytokine production, an effect that is partially blocked by anti-TGF-beta1. These results show that Smad7 blockade of TGF-beta1 signaling helps maintain the chronic production of proinflammatory cytokines that drives the inflammatory process in IBD and that inhibition of Smad7 enables endogenous TGF-beta to downregulate this response.
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Cites
Inflammatory bowel disease: Etiology and pathogenesis
Fiocchi, C. (1998) · Gastroenterology · doi:10.1016/s0016-5085(98)70381-6 · Cited by 2,059
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Cytokines in inflammatory bowel disease
Neurath, M. F. (2014) · Nature Reviews Immunology · doi:10.1038/nri3661 · Cited by 2,706
Immunopathogenesis of IBD: current state of the art
de Souza, H. S. P., & Fiocchi, C. (2016) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2015.186 · Cited by 1,551
TGF-β Activation and Function in Immunity
Travis, M. A., & Sheppard, D. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120257 · Cited by 856
Transforming growth factor-β in T-cell biology
Gorelik, L., & Flavell, R. A. (2002) · Nature Reviews Immunology · doi:10.1038/nri704 · Cited by 792
Role of cytokines in inflammatory bowel disease
Sanchez-Muñoz, F., Dominguez-Lopez, A., & Yamamoto-Furusho, J. K. (2008) · World Journal of Gastroenterology · doi:10.3748/wjg.14.4280 · Cited by 699
Monteleone, I., Rizzo, A., Sarra, M., Sica, G., Sileri, P., Biancone, L., MacDonald, T. T., Pallone, F., & Monteleone, G. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.04.007 · Cited by 656
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Sugimoto, M. A., Sousa, L. P., Pinho, V., Perretti, M., & Teixeira, M. M. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00160 · Cited by 638
The IBD interactome: an integrated view of aetiology, pathogenesis and therapy
de Souza, H. S. P., Fiocchi, C., & Iliopoulos, D. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2017.110 · Cited by 447
Regulation of TGF-β Family Signaling by Inhibitory Smads
Miyazawa, K., & Miyazono, K. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a022095 · Cited by 439
Jenkins, B. J., Grail, D., Nheu, T., Najdovska, M., Wang, B., Waring, P., Inglese, M., McLoughlin, R. M., Jones, S. A., Topley, N., et al. (2005) · Nature Medicine · doi:10.1038/nm1282 · Cited by 308
Targeting TGF-β signaling in cancer
Katz, L. H., Li, Y., Chen, J.-S., Muñoz, N. M., Majumdar, A., Chen, J., & Mishra, L. (2013) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2013.782287 · Cited by 212
Bhagat, G., Naiyer, A. J., Shah, J. G., Harper, J., Jabri, B., Wang, T. C., Green, P. H. R., & Manavalan, J. S. (2008) · Journal of Clinical Investigation · doi:10.1172/jci30989 · Cited by 188
MicroRNA-155 Targets SMAD2 and Modulates the Response of Macrophages to Transforming Growth Factor-β
Louafi, F., Martinez-Nunez, R. T., & Sanchez-Elsner, T. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.146852 · Cited by 181
Next generation of small molecules in inflammatory bowel disease
Olivera, P., Danese, S., & Peyrin-Biroulet, L. (2017) · Gut · doi:10.1136/gutjnl-2016-312912 · Cited by 154
Human monocytes and macrophages regulate immune tolerance via integrin αvβ8–mediated TGFβ activation
Kelly, A., Gunaltay, S., McEntee, C. P., Shuttleworth, E. E., Smedley, C., Houston, S. A., Fenton, T. M., Levison, S., Mann, E. R., & Travis, M. A. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20171491 · Cited by 124
McCartney-Francis, N., Jin, W., & Wahl, S. M. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.6.3814 · Cited by 101
SMAD regulatory networks construct a balanced immune system
Malhotra, N., & Kang, J. (2013) · Immunology · doi:10.1111/imm.12076 · Cited by 92
Fenton, T. M., Kelly, A., Shuttleworth, E. E., Smedley, C., Atakilit, A., Powrie, F., Campbell, S., Nishimura, S. L., Sheppard, D., Levison, S., et al. (2017) · Mucosal Immunology · doi:10.1038/mi.2016.94 · Cited by 64
Metadata
- Authors
- Monteleone, G., Kumberova, A., Croft, N. M., McKenzie, C., Steer, H. W., & MacDonald, T. T.
- Venue
- Journal of Clinical Investigation
- Published
- 2001-08-15
- Volume
- 108
- Issue
- 4
- Pages
- 601-609
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2026058763
- Cited by
- 600
- References
- 1
- FWCI
- 8.90
- Type
- journal article
- Language
- en
- Open access
- bronze
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