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Treg-specific IL-27R alpha deletion uncovers a key role for IL-27 in Treg function to control autoimmunity

Author(s)
Do, JeongsuKim, DongkyunKim, SoheeValentin-Torres, AliceDvorina, NinaJang, EunjungNagarajavel, VivekananthanDeSilva, Tara M.Li, XiaoxiaTing, Angela H.Vignali, Dario A. A.Stohlman, Stephen A.Baldwin, William M., IIIMin, Booki
Issued Date
2017-09
DOI
10.1073/pnas.1703100114
URI
https://scholarworks.unist.ac.kr/handle/201301/22776
Fulltext
http://www.pnas.org/content/114/38/10190
Citation
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.114, no.38, pp.10190 - 10195
Abstract
Dysregulated Foxp3(+) Treg functions result in uncontrolled immune activation and autoimmunity. Therefore, identifying cellular factors modulating Treg functions is an area of great importance. Here, using Treg-specific Il27ra(-/-) mice, we report that IL-27 signaling in Foxp3(+) Tregs is essential for Tregs to control autoimmune inflammation in the central nervous system (CNS). Following experimental autoimmune encephalomyelitis (EAE) induction, Treg-specific Il27ra-/- mice develop more severe EAE. Consistent with the severe disease, the numbers of IFN gamma- and IL-17-producing CD4 T cells infiltrating the CNS tissues are greater in these mice. Treg accumulation in the inflamed CNS tissues is not affected by the lack of IL-27 signaling in Tregs, suggesting a functional defect of Il27ra(-/-) Tregs. IL-10 production by conventional CD4 T cells and their CNS accumulation are rather elevated in Treg-specific Il27ra(-/-) mice. Analysis with Treg fate-mapping reporter mice further demonstrates that IL-27 signaling in Tregs may control stability of Foxp3 expression. Finally, systemic administration of recombinant IL-27 in Treg-specific Il27ra(-/-) mice fails to ameliorate the disease even in the presence of IL-27-responsive conventional CD4 T cells. These findings uncover a previously unknown role of IL-27 in regulating Treg function to control autoimmune inflammation.
Publisher
NATL ACAD SCIENCES
ISSN
0027-8424
Keyword (Author)
autoimmunityFoxp3+regulatory T cellsIL-27Tr1 cells
Keyword
REGULATORY T-CELLSCENTRAL-NERVOUS-SYSTEMDENDRITIC CELLSTH17 CELLSMULTIPLE-SCLEROSISSUPPRESSIONINTERLEUKIN-27EXPRESSIONENCEPHALOMYELITISINFLAMMATION

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