The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Blockade of interleukin-6 signaling augments regulatory T-cell reconstitution and attenuates the severity of graft-versus-host disease
Open accessAbstract
Graft-versus-host disease (GVHD) is the major complication after allogeneic bone marrow transplantation and is characterized by the overproduction of proinflammatory cytokines. In this study, we have identified interleukin-6 (IL-6) as a critical inflammatory cytokine that alters the balance between the effector and regulatory arms of the immune system and drives a proinflammatory phenotype that is a defining characteristic of GVHD. Our results demonstrate that inhibition of the IL-6 signaling pathway by way of antibody-mediated blockade of the IL-6 receptor (IL-6R) markedly reduces pathologic damage attributable to GVHD. This is accompanied by a significant increase in the absolute number of regulatory T cells (Tregs) that is due to augmentation of thymic-dependent and thymic-independent Treg production. Correspondingly, there is a significant reduction in the number of T helper 1 and T helper 17 cells in GVHD target organs, demonstrating that blockade of IL-6 signaling decreases the ratio of proinflammatory T cells to Tregs. These studies demonstrate that antibody blockade of the IL-6R serves to recalibrate the effector and regulatory arms of the immune system and represents a novel, potentially clinically translatable, strategy for the attenuation of GVHD.
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Cites
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CD4+CD25+ Immunoregulatory T Cells
McHugh, R. S., Whitters, M. J., Piccirillo, C. A., Young, D. A., Shevach, E. M., Collins, M., & Byrne, M. C. (2002) · Immunity · doi:10.1016/s1074-7613(02)00280-7 · Cited by 1,395
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Cited by
Cooke, K. R., Luznik, L., Sarantopoulos, S., Hakim, F. T., Jagasia, M., Fowler, D. H., van den Brink, M. R. M., Hansen, J. A., Parkman, R., Miklos, D. B., et al. (2017) · Biology of Blood and Marrow Transplantation · doi:10.1016/j.bbmt.2016.09.023 · Cited by 472
Essentials of Th17 cell commitment and plasticity
Muranski, P., & Restifo, N. P. (2013) · Blood · doi:10.1182/blood-2012-09-378653 · Cited by 383
Nucleoside reverse transcriptase inhibitors possess intrinsic anti-inflammatory activity
Fowler, B. J., Gelfand, B. D., Kim, Y., Kerur, N., Tarallo, V., Hirano, Y., Amarnath, S., Fowler, D. H., Radwan, M., Young, M. T., et al. (2014) · Science · doi:10.1126/science.1261754 · Cited by 225
Laurence, A., Amarnath, S., Mariotti, J., Kim, Y. C., Foley, J., Eckhaus, M., O'Shea, J. J., & Fowler, D. H. (2012) · Immunity · doi:10.1016/j.immuni.2012.05.027 · Cited by 201
The role of microbiota in allogeneic hematopoietic stem cell transplantation
Chang, C.-C., Hayase, E., & Jenq, R. R. (2021) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2021.1872541 · Cited by 20
Metadata
- Authors
- Chen, X., Das, R., Komorowski, R., Beres, A., Hessner, M. J., Mihara, M., & Drobyski, W. R.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2009-07-23
- Volume
- 114
- Issue
- 4
- Pages
- 891-900
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1974508346
- Cited by
- 293
- References
- 5
- FWCI
- 11.69
- Type
- journal article
- Language
- en
- Open access
- green
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- Chen, X., Das, R., Komorowski, R., Beres, A., Hessner, M. J., Mihara, M., & Drobyski, W. R. (2009). Blockade of interleukin-6 signaling augments regulatory T-cell reconstitution and attenuates the severity of graft-versus-host disease. Blood. https://doi.org/10.1182/blood-2009-01-197178
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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.
