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The Transcription Factor T-bet Regulates Intestinal Inflammation Mediated by Interleukin-7 Receptor+ Innate Lymphoid Cells
Open accessAbstract
Mice lacking the transcription factor T-bet in the innate immune system develop microbiota-dependent colitis. Here, we show that interleukin-17A (IL-17A)-producing IL-7Rα(+) innate lymphoid cells (ILCs) were potent promoters of disease in Tbx21(-/-)Rag2(-/-) ulcerative colitis (TRUC) mice. TNF-α produced by CD103(-)CD11b(+) dendritic cells synergized with IL-23 to drive IL-17A production by ILCs, demonstrating a previously unrecognized layer of cellular crosstalk between dendritic cells and ILCs. We have identified Helicobacter typhlonius as a key disease trigger driving excess TNF-α production and promoting colitis in TRUC mice. Crucially, T-bet also suppressed the expression of IL-7R, a key molecule involved in controlling intestinal ILC homeostasis. The importance of IL-7R signaling in TRUC disease was highlighted by the dramatic reduction in intestinal ILCs and attenuated colitis following IL-7R blockade. Taken together, these data demonstrate the mechanism by which T-bet regulates the complex interplay between mucosal dendritic cells, ILCs, and the intestinal microbiota.
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Greengenes, a Chimera-Checked 16S rRNA Gene Database and Workbench Compatible with ARB
DeSantis, T. Z., Hugenholtz, P., Larsen, N., Rojas, M., Brodie, E. L., Keller, K., Huber, T., Dalevi, D., Hu, P., & Andersen, G. L. (2006) · Applied and Environmental Microbiology · doi:10.1128/aem.03006-05 · Cited by 10,891
Dysbiosis of the faecal microbiota in patients with Crohn’s disease and their unaffected relatives
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Self-citationLupp, C., Robertson, M. L., Wickham, M. E., Sekirov, I., Champion, O. L., Gaynor, E. C., & Finlay, B. B. (2007) · Cell Host & Microbe · doi:10.1016/j.chom.2007.08.002 · Cited by 501
Cited by
Role of the microbiota in immunity and inflammation.
Belkaid, Y., & Hand, T. W. (2014) · Cell · doi:10.1016/j.cell.2014.03.011 · Cited by 5,385
Proteobacteria: Microbial signature of dysbiosis in gut microbiota
Shin, N.-R., Whon, T. W., & Bae, J.-W. (2015) · Trends in Biotechnology · doi:10.1016/j.tibtech.2015.06.011 · Cited by 3,954
Innate lymphoid cells — a proposal for uniform nomenclature
Spits, H., Artis, D., Colonna, M., Diefenbach, A., Di Santo, J. P., Eberl, G., Koyasu, S., Locksley, R. M., McKenzie, A. N. J., Mebius, R. E., et al. (2013) · Nature Reviews Immunology · doi:10.1038/nri3365 · Cited by 2,389
Role of the gut microbiota in immunity and inflammatory disease
Kamada, N., Seo, S.-U., Chen, G. Y., & Núñez, G. (2013) · Nature reviews. Immunology · doi:10.1038/nri3430 · Cited by 2,256
The microbiome and innate immunity
Thaiss, C. A., Zmora, N., Levy, M., & Elinav, E. (2016) · Nature · doi:10.1038/nature18847 · Cited by 2,012
Metadata
- Authors
- Powell, N., Walker, A. W., Stolarczyk, E., Canavan, J. B., Gökmen, M. R., Marks, E., Jackson, I., Hashim, A., Curtis, M. A., Jenner, R. G., Howard, J. K., Parkhill, J., MacDonald, T. T., & Lord, G. M.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2012-10
- Volume
- 37
- Issue
- 4
- Pages
- 674-684
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2028057905
- Cited by
- 324
- References
- 4
- FWCI
- 13.07
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Powell, N., Walker, A. W., Stolarczyk, E., Canavan, J. B., Gökmen, M. R., Marks, E., Jackson, I., Hashim, A., Curtis, M. A., Jenner, R. G., Howard, J. K., Parkhill, J., MacDonald, T. T., & Lord, G. M. (2012). The Transcription Factor T-bet Regulates Intestinal Inflammation Mediated by Interleukin-7 Receptor+ Innate Lymphoid Cells. Immunity. https://doi.org/10.1016/j.immuni.2012.09.008
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
