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Cited by 503T-cell and B-cell ImmunologyInflammatory Bowel DiseaseCell Adhesion Molecules Research

Loss of integrin αvβ8 on dendritic cells causes autoimmunity and colitis in mice

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Travis, Mark A., Reizis, Boris, Melton, Andrew C., Masteller, Emma, Tang, Qizhi, Proctor, John M., Wang, Yanli, Bernstein, Xin +4 more·2007·Nature
DOI 10.1038/nature06110PMC PMC2670239
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Abstract

The cytokine transforming growth factor-beta (TGF-beta) is an important negative regulator of adaptive immunity. TGF-beta is secreted by cells as an inactive precursor that must be activated to exert biological effects, but the mechanisms that regulate TGF-beta activation and function in the immune system are poorly understood. Here we show that conditional loss of the TGF-beta-activating integrin alpha(v)beta8 on leukocytes causes severe inflammatory bowel disease and age-related autoimmunity in mice. This autoimmune phenotype is largely due to lack of alpha(v)beta8 on dendritic cells, as mice lacking alpha(v)beta8 principally on dendritic cells develop identical immunological abnormalities as mice lacking alpha(v)beta8 on all leukocytes, whereas mice lacking alpha(v)beta8 on T cells alone are phenotypically normal. We further show that dendritic cells lacking alpha(v)beta8 fail to induce regulatory T cells (T(R) cells) in vitro, an effect that depends on TGF-beta activity. Furthermore, mice lacking alpha(v)beta8 on dendritic cells have reduced proportions of T(R) cells in colonic tissue. These results suggest that alpha(v)beta8-mediated TGF-beta activation by dendritic cells is essential for preventing immune dysfunction that results in inflammatory bowel disease and autoimmunity, effects that are due, at least in part, to the ability of alpha(v)beta8 on dendritic cells to induce and/or maintain tissue T(R) cells.

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Cited by

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Authors
Travis, M. A., Reizis, B., Melton, A. C., Masteller, E., Tang, Q., Proctor, J. M., Wang, Y., Bernstein, X., Huang, X., Reichardt, L. F., Bluestone, J. A., & Sheppard, D.
Affiliations
  • University of California, San Francisco (US)
  • Columbia University (US)
  • University of San Francisco (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Sheppard, Dean
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2007-08-12
Volume
449
Issue
7160
Pages
361-365
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature06110
PMC
PMC2670239
OpenAlex
W1584463243
Cited by
503
References
2
Citations by year
2026: 9 · 2025: 11 · 2024: 12 · 2023: 15 · 2022: 13 · 2021: 23 · 2020: 23 · 2019: 34 · 2018: 21 · 2017: 36 · 2016: 30 · 2015: 25 · 2014: 22 · 2013: 35 · 2012: 31
FWCI
15.13
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • Research Explorer (The University of Manchester) (submittedVersion)
Funders
National Institute of Neurological Disorders and Stroke (R01NS019090)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Keywords
integrin αvβ8, dendritic cells, TGF-beta activation, regulatory T cells, colitis, inflammatory bowel disease, autoimmunity, immune tolerance, conditional knockout mice, colonic inflammation
MeSH terms
Aging, Animals, Colitis, Colon, Dendritic Cells, Immunoglobulins, Immunologic Memory, Interferon-gamma, Leukocytes, Lymphocyte Activation, Phenotype, Autoimmunity, Interleukin-4, Integrins, Transforming Growth Factor beta, Lymphocyte Count, T-Lymphocytes, Regulatory, Mice

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