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Scientific article
English

IL-27 Induces Th17 Differentiation in the Absence of STAT1 Signaling

Contributors

Peters, Anneli; Fowler, Kevin D; Chalmin, Fanny; Merkler, Doron; Kuchroo, Vijay K; Pot, Caroline

Published in

The Journal of immunology, vol. 195, no. 9, p. 4144-4153

Publication date

2015

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.

UNIGE affiliation entities

UNIGE research groups

Citation (ISO format)

PETERS, Anneli et al. IL-27 Induces Th17 Differentiation in the Absence of STAT1 Signaling. In: The Journal of immunology, 2015, vol. 195, n° 9, p. 4144–4153. doi: 10.4049/jimmunol.1302246

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Article (Published version)

Identifiers

Journal ISSN

0022-1767
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Technical informations

Creation

08/10/2015 16:47:00

First validation

08/10/2015 16:47:00

Update

13/10/2025 21:09:30

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14/03/2023 23:53:59

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