Cutting edge: TNF receptor-associated factor 4 restricts IL-17-mediated pathology and signaling processes

Jarod A Zepp; Caini Liu; Wen Qian; Ling Wu; Muhammet F Gulen; Zizhen Kang; Xiaoxia Li

doi:10.4049/jimmunol.1200470

Back

Cutting edge: TNF receptor-associated factor 4 restricts IL-17-mediated pathology and signaling processes

Journal article

Peer reviewed

Cutting edge: TNF receptor-associated factor 4 restricts IL-17-mediated pathology and signaling processes

Jarod A Zepp, Caini Liu, Wen Qian, Ling Wu, Muhammet F Gulen, Zizhen Kang and Xiaoxia Li

The Journal of immunology (1950), Vol.189(1), pp.33-37

07/01/2012

DOI: 10.4049/jimmunol.1200470

PMCID: PMC3590847

PMID: 22649194

View Online

Abstract

The effector T cell subset, Th17, plays a significant role in the pathogenesis of multiple sclerosis and of other autoimmune diseases. The signature cytokine, IL-17, engages the IL-17R and recruits the E3-ligase NF-κB activator 1 (Act1) upon stimulation. In this study, we examined the role of TNFR-associated factor (TRAF)4 in IL-17 signaling and Th17-mediated autoimmune encephalomyelitis. Primary cells from TRAF4-deficient mice displayed markedly enhanced IL-17-activated signaling pathways and induction of chemokine mRNA. Adoptive transfer of MOG35-55 specific wild-type Th17 cells into TRAF4-deficient recipient mice induced an earlier onset of disease. Mechanistically, we found that TRAF4 and TRAF6 used the same TRAF binding sites on Act1, allowing the competition of TRAF4 with TRAF6 for the interaction with Act1. Taken together, the results of this study reveal the necessity of a unique role of TRAF4 in restricting the effects of IL-17 signaling and Th17-mediated disease.

Animals

Encephalomyelitis, Autoimmune, Experimental - genetics

Encephalomyelitis, Autoimmune, Experimental - immunology

Encephalomyelitis, Autoimmune, Experimental - pathology

HEK293 Cells

HeLa Cells

Humans

Interleukin-17 - antagonists & inhibitors

Interleukin-17 - genetics

Interleukin-17 - physiology

Mice

Mice, Inbred C57BL

Mice, Knockout

RNA, Messenger - biosynthesis

Signal Transduction - genetics

Signal Transduction - immunology

Th17 Cells - immunology

Th17 Cells - pathology

TNF Receptor-Associated Factor 4 - deficiency

TNF Receptor-Associated Factor 4 - genetics

TNF Receptor-Associated Factor 4 - physiology

Details

Title: Subtitle: Cutting edge: TNF receptor-associated factor 4 restricts IL-17-mediated pathology and signaling processes
Creators: Jarod A Zepp - Cleveland Clinic
Caini Liu - Cleveland Clinic
Wen Qian - Cleveland Clinic
Ling Wu - Case Western Reserve University
Muhammet F Gulen - Cleveland Clinic
Zizhen Kang - Cleveland Clinic
Xiaoxia Li - Cleveland Clinic
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.189(1), pp.33-37
DOI: 10.4049/jimmunol.1200470
PMID: 22649194
PMCID: PMC3590847
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Grant note: UL1 RR024989 / NCRR NIH HHS P01HL103453 / NHLBI NIH HHS P01 HL103453 / NHLBI NIH HHS T32 GM007250 / NIGMS NIH HHS R01 NS071996 / NINDS NIH HHS T32 AI089474 / NIAID NIH HHS R01NS071996 / NINDS NIH HHS
Language: English
Date published: 07/01/2012
Academic Unit: Pathology; Iowa Neuroscience Institute
Record Identifier: 9984201118902771

Metrics

13 Record Views

63 Times Cited - Web of Science

See more details