CD28 suppresses IL-23- and IL-1β-driven human Th17 development
| Autor: | Mandy J. McGeachy, Shankar Revu, Jing Wu, Natalie Rittenhouse, Ashley Menk, Greg M. Delgoffe, Amanda C. Poholek |
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| Rok vydání: | 2018 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 200:164.1-164.1 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Th17 cells drive autoimmune disease but also control commensal microbes. A common link between antigens from self-proteins or commensal microbiota is relatively low activation of T cell receptor and costimulation signaling. Indeed, strong TCR/CD28 stimulation suppressed Th17 cell differentiation from human naïve T cells, but not effector/memory cells. CD28 suppressed the classical Th17 transcriptional program, while inducing known Th17-regulators, and acted through an Akt-dependent mechanism. Th17 cells differentiated without CD28 were not anergic: they showed robust proliferation and maintained Th17 cytokine production following restimulation. IL-23 and IL-1β promoted glucose uptake and increased glycolysis. Although modestly increased compared to CD28 costimulation, glycolysis was necessary to support Th17 differentiation, indicating that cytokine-mediated metabolic shifts were sufficient to obviate the classical requirement for CD28 in Th17 differentiation. Together these data propose that in humans, strength of TCR/CD28/Akt activation serves as a rheostat tuning the magnitude of Th17 development driven by IL-23 and IL-1β. |
| Databáze: | OpenAIRE |
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