Nish, Simone A., Schenten, Dominik, Wunderlich, F. Thomas, Pope, Scott, Gao, Yan, Hoshi, Namiko, Yu, Shuang, Yan, Xiting, Lee, Heung Kyu ORCID: 0000-0002-3977-1510, Pasman, Lesley, Brodsky, Igor, Yordy, Brian, Zhao, Hongyu, Bruening, Jens C. and Medzhitov, Ruslan (2014). T cell-intrinsic role of IL-6 signaling in primary and memory responses. eLife, 3. CAMBRIDGE: ELIFE SCIENCES PUBLICATIONS LTD. ISSN 2050-084X

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Abstract

Innate immune recognition is critical for the induction of adaptive immune responses; however the underlying mechanisms remain incompletely understood. Here, we demonstrate that T cell-specific deletion of the IL-6 receptor a chain (IL-6R alpha) results in impaired Th1 and Th17 T cell responses in vivo, and a defect in the Tfh function. Depletion of Tregs in these mice rescued the Th1 but not the Th17 response. Our data suggest that IL-6 signaling in effector T cells is required to overcome Treg-mediated suppression in vivo. We show that IL-6 cooperates with IL-1 beta to block the suppressive effect of Tregs on CD4(+) T cells, at least in part by controlling their responsiveness to IL-2. In addition, although IL-6R alpha-deficient T cells mount normal primary Th1 responses in the absence of Tregs, they fail to mature into functional memory cells, demonstrating a key role for IL-6 in CD4+ T cell memory formation.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Nish, Simone A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schenten, DominikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wunderlich, F. ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pope, ScottUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gao, YanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoshi, NamikoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yu, ShuangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yan, XitingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lee, Heung KyuUNSPECIFIEDorcid.org/0000-0002-3977-1510UNSPECIFIED
Pasman, LesleyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brodsky, IgorUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yordy, BrianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhao, HongyuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruening, Jens C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Medzhitov, RuslanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-438258
DOI: 10.7554/eLife.01949
Journal or Publication Title: eLife
Volume: 3
Date: 2014
Publisher: ELIFE SCIENCES PUBLICATIONS LTD
Place of Publication: CAMBRIDGE
ISSN: 2050-084X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
TRANSCRIPTION FACTOR FOXP3; FOLLICULAR-HELPER-CELLS; GROWTH-FACTOR-BETA; IMMUNE-RESPONSES; MEDIATED SUPPRESSION; DENDRITIC CELLS; DIFFERENTIATION; GENERATION; INTERLEUKIN-6; RECEPTORMultiple languages
BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/43825

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