The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Rapamycin inhibits IL-4—induced dendritic cell maturation in vitro and dendritic cell mobilization and function in vivo
Abstract
Rapamycin (RAPA) is a potent immunosuppressive macrolide hitherto believed to mediate its action primarily via suppression of lymphocyte responses to interleukin 2 (IL-2) and other growth factors. We show here that this view is incomplete and provide evidence that RAPA suppresses the functional activation of dendritic cells (DCs) both in vitro and in vivo. In vitro, RAPA inhibits IL-4—dependent maturation and T-cell stimulatory activity of murine bone marrow—derived DCs. These effects are associated with posttranscriptional down-regulation of both subunits of the IL-4 receptor complex (CD124, CD132) and are mediated via binding of RAPA to its intracellular receptor FK506-binding protein 12 (FKBP12). In vivo, RAPA impairs steady-state DC generation and fms-like tyrosine 3 kinase ligand (Flt3L)—induced DC mobilization. In addition, in vivo administration of RAPA impairs DC costimulatory molecule up-regulation, production of proinflammatory cytokines, and T-cell allostimulatory capacity. These novel findings have implications for RAPA-based therapy of chronic DC-triggered autoimmune diseases, transplant rejection, and hematologic malignancies with activating Flt3 mutations.
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Cites
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Cited by
Immunoregulatory functions of mTOR inhibition
Thomson, A. W., Turnquist, H. R., & Raimondi, G. (2009) · Nature Reviews Immunology · doi:10.1038/nri2546 · Cited by 847
Self-citationRegulation of Immune Responses by mTOR
Powell, J. D., Pollizzi, K. N., Heikamp, E. B., & Horton, M. R. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075024 · Cited by 836
Regulation of innate immune cell function by mTOR
Weichhart, T., Hengstschläger, M., & Linke, M. (2015) · Nature Reviews Immunology · doi:10.1038/nri3901 · Cited by 830
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Self-citationTargeting mammalian target of rapamycin (mTOR) for health and diseases
Tsang, C. K., Qi, H., Liu, L. F., & Zheng, X. F. S. (2007) · Drug Discovery Today · doi:10.1016/j.drudis.2006.12.008 · Cited by 406
Metadata
- Authors
- Hackstein, H., Taner, T., Zahorchak, A. F., Morelli, A. E., Logar, A. J., Gessner, A., & Thomson, A. W.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2003-06-01
- Volume
- 101
- Issue
- 11
- Pages
- 4457-4463
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2010665897
- Cited by
- 381
- References
- 45
- FWCI
- 6.03
- Type
- journal article
- Language
- en
- Open access
- closed
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