The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Mammalian target of rapamycin and glycogen synthase kinase 3 differentially regulate lipopolysaccharide-induced interleukin-12 production in dendritic cells
Open accessAbstract
Phosphoinositide 3-kinase (PI3K) negatively regulates Toll-like receptor (TLR)–mediated interleukin-12 (IL-12) expression in dendritic cells (DCs). We show here that 2 signaling pathways downstream of PI3K, mammalian target of rapamycin (mTOR) and glycogen synthase kinase 3 (GSK3), differentially regulate the expression of IL-12 in lipopolysaccharide (LPS)–stimulated DCs. Rapamycin, an inhibitor of mTOR, enhanced IL-12 production in LPS-stimulated DCs, whereas the activation of mTOR by lentivirus-mediated transduction of a constitutively active form of Rheb suppressed the production of IL-12. The inhibition of protein secretion or deletion of IL-10 cancelled the effect of rapamycin, indicating that mTOR regulates IL-12 expression through an autocrine action of IL-10. In contrast, GSK3 positively regulates IL-12 production through an IL-10–independent pathway. Rapamycin-treated DCs enhanced Th1 induction in vitro compared with untreated DCs. LiCl, an inhibitor of GSK3, suppressed a Th1 response on Leishmania major infection in vivo. These results suggest that mTOR and GSK3 pathways regulate the Th1/Th2 balance though the regulation of IL-12 expression in DCs. The signaling pathway downstream of PI3K would be a good target to modulate the Th1/Th2 balance in immune responses in vivo.
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Cites
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Cited by
Metabolic reprogramming in macrophages and dendritic cells in innate immunity
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mTOR regulates memory CD8 T-cell differentiation
Araki, K., Turner, A. P., Shaffer, V. O., Gangappa, S., Keller, S. A., Bachmann, M. F., Larsen, C. P., & Ahmed, R. (2009) · Nature · doi:10.1038/nature08155 · Cited by 1,575
Toll-like receptor–induced changes in glycolytic metabolism regulate dendritic cell activation
Krawczyk, C. M., Holowka, T., Sun, J., Blagih, J., Amiel, E., DeBerardinis, R. J., Cross, J. R., Jung, E., Thompson, C. B., Jones, R. G., et al. (2010) · Blood · doi:10.1182/blood-2009-10-249540 · Cited by 1,246
Biology and therapeutic potential of interleukin-10
Saraiva, M., Vieira, P., & O’Garra, A. (2020) · Journal of Experimental Medicine · doi:10.1084/jem.20190418 · Cited by 1,118
Regulation 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
Metadata
- Authors
- Ohtani, M., Nagai, S., Kondo, S., Mizuno, S., Nakamura, K., Tanabe, M., Takeuchi, T., Matsuda, S., & Koyasu, S.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2008-08-01
- Volume
- 112
- Issue
- 3
- Pages
- 635-643
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2069089745
- Cited by
- 265
- References
- 8
- FWCI
- 8.84
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Ohtani, M., Nagai, S., Kondo, S., Mizuno, S., Nakamura, K., Tanabe, M., Takeuchi, T., Matsuda, S., & Koyasu, S. (2008). Mammalian target of rapamycin and glycogen synthase kinase 3 differentially regulate lipopolysaccharide-induced interleukin-12 production in dendritic cells. Blood. https://doi.org/10.1182/blood-2008-02-137430
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