The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
The IL23R R381Q Gene Variant Protects against Immune-Mediated Diseases by Impairing IL-23-Induced Th17 Effector Response in Humans
Open accessAbstract
IL-23 and Th17 cells are key players in tissue immunosurveillance and are implicated in human immune-mediated diseases. Genome-wide association studies have shown that the IL23R R381Q gene variant protects against psoriasis, Crohn's disease and ankylosing spondylitis. We investigated the immunological consequences of the protective IL23R R381Q gene variant in healthy donors. The IL23R R381Q gene variant had no major effect on Th17 cell differentiation as the frequency of circulating Th17 cells was similar in carriers of the IL23R protective (A) and common (G) allele. Accordingly, Th17 cells generated from A and G donors produced similar amounts of Th17 cytokines. However, IL-23-mediated Th17 cell effector function was impaired, as Th17 cells from A allele carriers had significantly reduced IL-23-induced IL-17A production and STAT3 phosphorylation compared to G allele carriers. Our functional analysis of a human disease-associated gene variant demonstrates that IL23R R381Q exerts its protective effects through selective attenuation of IL-23-induced Th17 cell effector function without interfering with Th17 differentiation, and highlights its importance in the protection against IL-23-induced tissue pathologies.
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IL-23 drives a pathogenic T cell population that induces autoimmune inflammation
Langrish, C. L., Chen, Y., Blumenschein, W. M., Mattson, J., Basham, B., Sedgwick, J. D., McClanahan, T., Kastelein, R. A., & Cua, D. J. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20041257 · Cited by 4,099
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Phenotypic and functional features of human Th17 cells
Annunziato, F., Cosmi, L., Santarlasci, V., Maggi, L., Liotta, F., Mazzinghi, B., Parente, E., Filì, L., Ferri, S., Frosali, F., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070663 · Cited by 1,861
Acosta-Rodriguez, E. V., Napolitani, G., Lanzavecchia, A., & Sallusto, F. (2007) · Nature Immunology · doi:10.1038/ni1496 · Cited by 1,857
Divergent Pro- and Antiinflammatory Roles for IL-23 and IL-12 in Joint Autoimmune Inflammation
Murphy, C. A., Langrish, C. L., Chen, Y., Blumenschein, W., McClanahan, T., Kastelein, R. A., Sedgwick, J. D., & Cua, D. J. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030896 · Cited by 1,669
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Interleukin-23 drives innate and T cell–mediated intestinal inflammation
Hue, S., Ahern, P., Buonocore, S., Kullberg, M. C., Cua, D. J., McKenzie, B. S., Powrie, F., & Maloy, K. J. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20061099 · Cited by 823
Cited by
Lowes, M. A., Suárez-Fariñas, M., & Krueger, J. G. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120225 · Cited by 1,650
Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity
Collaborative Association Study of Psoriasis (CASP), Tsoi, L. C., Genetic Analysis of Psoriasis Consortium, Psoriasis Association Genetics Extension, Wellcome Trust Case Control Consortium 2, Spain, S. L., Knight, J., Ellinghaus, E., Stuart, P. E., Capon, F., et al. (2012) · Nature Genetics · doi:10.1038/ng.2467 · Cited by 1,024
Self-citationTeng, M. W. L., Bowman, E. P., McElwee, J. J., Smyth, M. J., Casanova, J.-L., Cooper, A. M., & Cua, D. J. (2015) · Nature Medicine · doi:10.1038/nm.3895 · Cited by 873
National Institute of Diabetes and Digestive Kidney Diseases Inflammatory Bowel Disease Genetics Consortium (NIDDK IBDGC), Rivas, M. A., United Kingdom Inflammatory Bowel Disease Genetics Consortium, International Inflammatory Bowel Disease Genetics Consortium, Beaudoin, M., Gardet, A., Stevens, C., Sharma, Y., Zhang, C. K., Boucher, G., et al. (2011) · Nature Genetics · doi:10.1038/ng.952 · Cited by 771
Therapeutics targeting the IL-23 and IL-17 pathway in psoriasis
Ghoreschi, K., Balato, A., Enerbäck, C., & Sabat, R. (2021) · The Lancet · doi:10.1016/s0140-6736(21)00184-7 · Cited by 668
Metadata
- Authors
- Di Meglio, P., Di Cesare, A., Laggner, U., Chu, C.-C., Napolitano, L., Villanova, F., Tosi, I., Capon, F., Trembath, R. C., Peris, K., & Nestle, F. O.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-02-22
- Volume
- 6
- Issue
- 2
- Pages
- e17160
- ISSN
- 1932-6203 (ISSN-L)
- OpenAlex
- W1979011193
- Cited by
- 262
- References
- 8
- FWCI
- 10.80
- Type
- journal article
- Language
- en
- Open access
- gold
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- Di Meglio, P., Di Cesare, A., Laggner, U., Chu, C.-C., Napolitano, L., Villanova, F., Tosi, I., Capon, F., Trembath, R. C., Peris, K., & Nestle, F. O. (2011). The IL23R R381Q Gene Variant Protects against Immune-Mediated Diseases by Impairing IL-23-Induced Th17 Effector Response in Humans. PLoS ONE. https://doi.org/10.1371/journal.pone.0017160
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