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unige:77899 
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IL-27 Induces Th17 Differentiation in the Absence of STAT1 Signaling |
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| Published in | Journal of Immunology. 2015, vol. 195, no. 9, p. 4144-4153 | |
| Abstract | It is known that differentiation of Th17 cells is promoted by activation of STAT3 and inhibited by activation of STAT1. Although both transcription factors are activated by several cytokines, including IL-6, IL-21, and IL-27, each of these cytokines has a very different effect on Th17 differentiation, ranging from strong induction (IL-6) to strong inhibition (IL-27). To determine the molecular basis for these differences, we measured STAT3 and STAT1 activation profiles for IL-6, IL-21, and IL-27, as well as for cytokine pairs over time. We found that the ratio of activated STAT3/activated STAT1 is crucial in determining whether cytokines promote or inhibit Th17 differentiation. IL-6 and IL-21 induced p-STAT3/p-STAT1 ratios > 1, leading to the promotion of Th17 differentiation, whereas IL-27 or IL-6+IL-27 induced p-STAT3/p-STAT1 ratios < 1, resulting in inhibition of Th17 differentiation. Consistent with these findings, we show that IL-27 induces sufficient p-STAT3 to promote Th17 differentiation in the absence of STAT1. Furthermore, IL-27-induced STAT1-deficient T cells were indistinguishable from bona fide highly proinflammatory Th17 cells because they induced severe experimental autoimmune encephalomyelitis upon adoptive transfer. Our results suggest that the ratio of p-STAT3/p-STAT1 induced by a cytokine or cytokine pairs can be used to predict whether they induce a competent Th17-differentiation program. | |
| Identifiers | PMID: 26408664 | |
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| Research group | La Sclérose en plaques (908) | |
| Citation (ISO format) | PETERS, Anneli et al. IL-27 Induces Th17 Differentiation in the Absence of STAT1 Signaling. In: Journal of Immunology, 2015, vol. 195, n° 9, p. 4144-4153. https://archive-ouverte.unige.ch/unige:77899 |
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