The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
T cell self-reactivity forms a cytokine milieu for spontaneous development of IL-17+ Th cells that cause autoimmune arthritis
Open accessAbstract
This report shows that highly self-reactive T cells produced in mice as a result of genetically altered thymic T cell selection spontaneously differentiate into interleukin (IL)-17–secreting CD4+ helper T (Th) cells (Th17 cells), which mediate an autoimmune arthritis that clinically and immunologically resembles rheumatoid arthritis (RA). The thymus-produced self-reactive T cells, which become activated in the periphery via recognition of major histocompatibility complex/self-peptide complexes, stimulate antigen-presenting cells (APCs) to secrete IL-6. APC-derived IL-6, together with T cell–derived IL-6, drives naive self-reactive T cells to differentiate into arthritogenic Th17 cells. Deficiency of either IL-17 or IL-6 completely inhibits arthritis development, whereas interferon (IFN)-γ deficiency exacerbates it. The generation, differentiation, and persistence of arthritogenic Th17 cells per se are, however, insufficient for producing overt autoimmune arthritis. Yet overt disease is precipitated by further expansion and activation of autoimmune Th17 cells, for example, via IFN-γ deficiency, homeostatic proliferation, or stimulation of innate immunity by microbial products. Thus, a genetically determined T cell self-reactivity forms a cytokine milieu that facilitates preferential differentiation of self-reactive T cells into Th17 cells. Extrinsic or intrinsic stimuli further expand these cells, thereby triggering autoimmune disease. Intervention in these events at cellular and molecular levels is useful to treat and prevent autoimmune disease, in particular RA.
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A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17
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IL-23 drives a pathogenic T cell population that induces autoimmune inflammation
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Transforming growth factor-β induces development of the TH17 lineage
Mangan, P. R., Harrington, L. E., O'Quinn, D. B., Helms, W. S., Bullard, D. C., Elson, C. O., Hatton, R. D., Wahl, S. M., Schoeb, T. R., & Weaver, C. T. (2006) · Nature · doi:10.1038/nature04754 · Cited by 3,087
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Divergent Pro- and Antiinflammatory Roles for IL-23 and IL-12 in Joint Autoimmune Inflammation
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Cited by
Korn, T., Bettelli, E., Oukka, M., & Kuchroo, V. K. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132710 · Cited by 4,873
Functional Specialization of Interleukin-17 Family Members
Iwakura, Y., Ishigame, H., Saijo, S., & Nakae, S. (2011) · Immunity · doi:10.1016/j.immuni.2011.02.012 · Cited by 1,289
Self-citationLeibundGut-Landmann, S., Groß, O., Robinson, M. J., Osorio, F., Slack, E. C., Tsoni, S. V., Schweighoffer, E., Tybulewicz, V., Brown, G. D., Ruland, J., et al. (2007) · Nature Immunology · doi:10.1038/ni1460 · Cited by 1,191
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Self-citationThe Australo-Anglo-American Spondyloarthritis Consortium (TASC), Evans, D. M., the Wellcome Trust Case Control Consortium 2 (WTCCC2), Spondyloarthritis Research Consortium of Canada (SPARCC), Spencer, C. C. A., Pointon, J. J., Su, Z., Harvey, D., Kochan, G., Oppermann, U., et al. (2011) · Nature Genetics · doi:10.1038/ng.873 · Cited by 893
Metadata
- Authors
- Hirota, K., Hashimoto, M., Yoshitomi, H., Tanaka, S., Nomura, T., Yamaguchi, T., Iwakura, Y., Sakaguchi, N., & Sakaguchi, S.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2007-01-16
- Volume
- 204
- Issue
- 1
- Pages
- 41-47
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2101180663
- Cited by
- 482
- References
- 9
- FWCI
- 19.20
- Type
- journal article
- Language
- en
- Open access
- green
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- Hirota, K., Hashimoto, M., Yoshitomi, H., Tanaka, S., Nomura, T., Yamaguchi, T., Iwakura, Y., Sakaguchi, N., & Sakaguchi, S. (2007). T cell self-reactivity forms a cytokine milieu for spontaneous development of IL-17+ Th cells that cause autoimmune arthritis. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20062259
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