The Receptor SIGIRR Suppresses Th17 Cell Proliferation via Inhibition of the Interleukin-1 Receptor Pathway and mTOR Kinase Activation

Muhammet F Gulen; Zizhen Kang; Katarzyna Bulek; Wan Youzhong; Tae Whan Kim; Yi Chen; Cengiz Z Altuntas; Kristian Sass Bak-Jensen; Mandy J McGeachy; Jeong-Su Do; Hui Xiao; Greg M Delgoffe; Booki Min; Jonathan D Powell; Vincent K Tuohy; Daniel J Cua; Xiaoxia Li

doi:10.1016/j.immuni.2009.12.003

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The Receptor SIGIRR Suppresses Th17 Cell Proliferation via Inhibition of the Interleukin-1 Receptor Pathway and mTOR Kinase Activation

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The Receptor SIGIRR Suppresses Th17 Cell Proliferation via Inhibition of the Interleukin-1 Receptor Pathway and mTOR Kinase Activation

Muhammet F Gulen, Zizhen Kang, Katarzyna Bulek, Wan Youzhong, Tae Whan Kim, Yi Chen, Cengiz Z Altuntas, Kristian Sass Bak-Jensen, Mandy J McGeachy, Jeong-Su Do, …

Immunity (Cambridge, Mass.), Vol.32(1), pp.54-66

2010

DOI: 10.1016/j.immuni.2009.12.003

PMCID: PMC3015141

PMID: 20060329

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Abstract

Interleukin-1 (IL-1)-mediated signaling in T cells is essential for T helper 17 (Th17) cell differentiation. We showed here that SIGIRR, a negative regulator of IL-1 receptor and Toll-like receptor signaling, was induced during Th17 cell lineage commitment and governed Th17 cell differentiation and expansion through its inhibitory effects on IL-1 signaling. The absence of SIGIRR in T cells resulted in increased Th17 cell polarization in vivo upon myelin oligodendrocyte glycoprotein (MOG 35-55) peptide immunization. Recombinant IL-1 promoted a marked increase in the proliferation of SIGIRR-deficient T cells under an in vitro Th17 cell-polarization condition. Importantly, we detected increased IL-1-induced phosphorylation of JNK and mTOR kinase in SIGIRR-deficient Th17 cells compared to wild-type Th17 cells. IL-1-induced proliferation was abolished in mTOR-deficient Th17 cells, indicating the essential role of mTOR activation. Our results demonstrate an important mechanism by which SIGIRR controls Th17 cell expansion and effector function through the IL-1-induced mTOR signaling pathway. ► SIGIRR is induced during Th17 cell lineage commitment ► SIGIRR suppresses Th17 cell effector function via inhibition of IL-1 signaling ► IL-1-induced proliferation is abolished in mTOR-deficient Th17 cells ► SIGIRR suppresses Th17 cell proliferation via inhibition of mTOR activation

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Title: Subtitle: The Receptor SIGIRR Suppresses Th17 Cell Proliferation via Inhibition of the Interleukin-1 Receptor Pathway and mTOR Kinase Activation
Creators: Muhammet F Gulen - Cleveland Clinic
Zizhen Kang - Cleveland Clinic
Katarzyna Bulek - Cleveland Clinic
Wan Youzhong - Cleveland Clinic
Tae Whan Kim - Cleveland Clinic
Yi Chen - Schering-Plough
Cengiz Z Altuntas - Cleveland Clinic
Kristian Sass Bak-Jensen - Merck Research Laboratories (Schering-Plough Biopharma), 901 California Avenue, Palo Alto, CA 94304, USA
Mandy J McGeachy - Schering-Plough
Jeong-Su Do - Cleveland Clinic
Hui Xiao - Cleveland Clinic
Greg M Delgoffe - Johns Hopkins University School of Medicine
Booki Min - Cleveland Clinic
Jonathan D Powell - Johns Hopkins University School of Medicine
Vincent K Tuohy - Cleveland Clinic
Daniel J Cua - Schering-Plough
Xiaoxia Li - Cleveland Clinic
Resource Type: Journal article
Publication Details: Immunity (Cambridge, Mass.), Vol.32(1), pp.54-66
DOI: 10.1016/j.immuni.2009.12.003
PMID: 20060329
PMCID: PMC3015141
NLM abbreviation: Immunity
ISSN: 1074-7613
eISSN: 1097-4180
Publisher: Elsevier Inc
Language: English
Date published: 2010
Academic Unit: Pathology; Iowa Neuroscience Institute
Record Identifier: 9984201251802771

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