The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Defects in CTLA-4 are associated with abnormal regulatory T cell function in rheumatoid arthritis
Open accessAbstract
The ultimate goal for the treatment of autoimmunity is to restore immunological tolerance. Regulatory T cells (Treg) play a central role in immune tolerance, and Treg functional abnormalities have been identified in different autoimmune diseases, including rheumatoid arthritis (RA). We have previously shown that natural Treg from RA patients are competent at suppressing responder T cell proliferation but not cytokine production. Here, we explore the hypothesis that this Treg defect in RA is linked with abnormalities in the expression and function of CTLA-4. We demonstrate that CTLA-4 expression on Treg from RA patients was significantly reduced compared with healthy Treg and is associated with an increased rate of CTLA-4 internalization. Regulation of T cell receptor signaling by CTLA-4 was impaired in RA Treg and associated with delayed recruitment of CTLA-4 to the immunological synapse. Artificial induction of CTLA-4 expression on RA Treg restored their suppressive capacity. Furthermore, CTLA-4 blockade impaired healthy Treg suppression of T cell IFN-γ production, but not proliferation, thereby recapitulating the unique Treg defect in RA. Our results suggest that defects in CTLA-4 could contribute to abnormal Treg function in RA and may represent a target for therapy for inducing long-lasting remission.
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Cites
CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells
Liu, W., Putnam, A. L., Xu-yu, Z., Szot, G. L., Lee, M. R., Zhu, S., Gottlieb, P. A., Kapranov, P., Gingeras, T. R., de St. Groth, B. F., et al. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20060772 · Cited by 2,606
Allan, S. E., Crome, S. Q., Crellin, N. K., Passerini, L., Steiner, T. S., Bacchetta, R., Roncarolo, M. G., & Levings, M. K. (2007) · International Immunology · doi:10.1093/intimm/dxm014 · Cited by 872
Stummvoll, G. H., DiPaolo, R. J., Huter, E. N., Davidson, T. S., Glass, D., Ward, J. M., & Shevach, E. M. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.3.1908 · Cited by 170
Cited by
Prakken, B., Albani, S., & Martini, A. (2011) · The Lancet · doi:10.1016/s0140-6736(11)60244-4 · Cited by 771
CTLA-4 is expressed by human monocyte-derived dendritic cells and regulates their functions
Laurent, S., Carrega, P., Saverino, D., Piccioli, P., Camoriano, M., Morabito, A., Dozin, B., Fontana, V., Simone, R., Mortara, L., et al. (2010) · Human Immunology · doi:10.1016/j.humimm.2010.07.007 · Cited by 121
T Regulatory Cells in Bone Remodelling
Bozec, A., & Zaiss, M. M. (2017) · Current Osteoporosis Reports · doi:10.1007/s11914-017-0356-1 · Cited by 110
T-cell exhaustion: understanding the interface of chronic viral and autoinflammatory diseases
McKinney, E. F., & Smith, K. G. (2016) · Immunology & Cell Biology · doi:10.1038/icb.2016.81 · Cited by 36
Gossmann, J., Stolte, M., Lohoff, M., Yu, P., Moll, R., Finkernagel, F., Garn, H., Brendel, C., Bittner, A., Neubauer, A., et al. (2016) · PLOS ONE · doi:10.1371/journal.pone.0150411 · Cited by 11
Metadata
- Authors
- Flores-Borja, F., Jury, E. C., Mauri, C., & Ehrenstein, M. R.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2008-12-09
- Volume
- 105
- Issue
- 49
- Pages
- 19396-19401
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2079632471
- Cited by
- 312
- References
- 3
- FWCI
- 7.27
- Type
- journal article
- Language
- en
- Open access
- green
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- Flores-Borja, F., Jury, E. C., Mauri, C., & Ehrenstein, M. R. (2008). Defects in CTLA-4 are associated with abnormal regulatory T cell function in rheumatoid arthritis. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0806855105
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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