The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Absence of signaling into CD4+ cells via C3aR and C5aR enables autoinductive TGF-β1 signaling and induction of Foxp3+ regulatory T cells
Open accessAbstract
Signaling through the G protein–coupled receptors for the complement fragments C3a and C5a (C3aR and C5aR, respectively) by dendritic cells and CD4+ cells provides costimulatory and survival signals to effector T cells. Here we found that when signals from C3aR and C5aR were not transduced into CD4+ cells, signaling via the kinases PI(3)Kγ, Akt and mTOR ceased, activation of the kinase PKA increased, autoinductive signaling by transforming growth factor-β1 (TGF-β1) initiated and CD4+ T cells became Foxp3+ induced regulatory T cells (iTreg cells). Endogenous TGF-β1 suppressed signaling through C3aR and C5aR by preventing the production of C3a and C5a and upregulating C5L2, an alternative receptor for C5a. The absence of signaling via C3aR and C5aR resulted in lower expression of costimulatory molecules and interleukin 6 (IL-6) and more production of IL-10. The resulting iTreg cells exerted robust suppression, had enhanced stability and suppressed ongoing autoimmune disease. Antagonism of C3aR and C5aR can also induce functional human iTreg cells.
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Bettelli, E., Carrier, Y., Gao, W., Korn, T., Strom, T. B., Oukka, M., Weiner, H. L., & Kuchroo, V. K. (2006) · Nature · doi:10.1038/nature04753 · Cited by 6,992
Regulation and function of mTOR signalling in T cell fate decisions
Chi, H. (2012) · Nature Reviews Immunology · doi:10.1038/nri3198 · Cited by 1,035
Transient expression of FOXP3 in human activated nonregulatory CD4 + T cells
Wang, J., Ioan‐Facsinay, A., van der Voort, E. I. H., Huizinga, T. W. J., & Toes, R. E. M. (2007) · European Journal of Immunology · doi:10.1002/eji.200636435 · Cited by 1,011
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A complex interplay between Akt, TSC2 and the two mTOR complexes
Huang, J., & Manning, B. D. (2009) · Biochemical Society Transactions · doi:10.1042/bst0370217 · Cited by 724
Lalli, P. N., Strainic, M. G., Yang, M., Lin, F., Medof, M. E., & Heeger, P. S. (2008) · Blood · doi:10.1182/blood-2008-04-151068 · Cited by 271
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Transforming Growth Factor-β Signaling in Immunity and Cancer
Batlle, E., & Massagué, J. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.024 · Cited by 2,366
Complement System Part II: Role in Immunity
Merle, N. S., Noe, R., Halbwachs-Mecarelli, L., Fremeaux-Bacchi, V., & Roumenina, L. T. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00257 · Cited by 1,051
Overview of complement activation and regulation
Noris, M., & Remuzzi, G. (2013) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2013.08.001 · Cited by 864
PI3K signalling in inflammation
Hawkins, P. T., & Stephens, L. R. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2014.12.006 · Cited by 541
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Metadata
- Authors
- Strainic, M. G., Shevach, E. M., An, F., Lin, F., & Medof, M. E.
- Venue
- Nature Immunology
- Published
- 2012-12-23
- Volume
- 14
- Issue
- 2
- Pages
- 162-171
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W1972665743
- Cited by
- 302
- References
- 6
- FWCI
- 10.11
- Type
- journal article
- Language
- en
- Open access
- green
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