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

Details

Serval ID
serval:BIB_535CBA631B4D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
IL-27 Induces Th17 Differentiation in the Absence of STAT1 Signaling.
Journal
Journal of Immunology
Author(s)
Peters A., Fowler K.D., Chalmin F., Merkler D., Kuchroo V.K., Pot C.
ISSN
1550-6606 (Electronic)
ISSN-L
0022-1767
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
195
Number
9
Pages
4144-4153
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
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.
Pubmed
Web of science
Open Access
Yes
Create date
09/11/2015 13:58
Last modification date
20/08/2019 14:08
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