TRAF Regulation of IL-17 Cytokine Signaling.

Junjie Zhao,Shadi Swaidani,Katarzyna Bulek,Xiaoxia Li,Caini Liu

doi:10.3389/fimmu.2019.01293

Junjie Zhao, Shadi Swaidani + Show 3 more

Open Access

https://doi.org/10.3389/fimmu.2019.01293

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Abstract

Tumor necrosis factor receptor (TNFR)-associated factors or (TRAFs) are important mediators of Interleukin-17 (IL-17) cytokine signaling and contribute to driving tissue responses that are crucial for protective immunity but are often implicated in immunopathology. By amplifying tissue immune activity, IL-17 cytokine pathways contribute to maintaining barrier function as well as activation of innate and adaptive immunity necessary for host defense. IL-17 receptors signaling is orchestrated in part, by the engagement of TRAFs and the subsequent unlocking of downstream cellular machinery that can promote pathogen clearance or contribute to immune dysregulation, chronic inflammation, and disease. Originally identified as signaling adaptors for TNFR superfamily, TRAF proteins can mediate the signaling of a variety of intercellular and extracellular stimuli and have been shown to regulate the downstream activity of many cytokine receptors including receptors for IL-1β, IL-2, IL-6, IL-17, IL-18, IL-33, type I IFNs, type III IFNs, GM-CSF, M-CSF, and TGF-β Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I- like receptors, and C-type lectin receptors. This review will focus on discussing studies that reveal our current understanding of how TRAFs mediate and regulate biochemical activities downstream of the IL-17 cytokines signaling.

Highlights

University of New Jersey, United States Bin Li, Shanghai Jiao Tong University School of Medicine, China
Identified as signaling adaptors for Tumor necrosis factor receptor (TNFR) superfamily, TRAF proteins can mediate the signaling of a variety of intercellular and extracellular stimuli and have been shown to regulate the downstream activity of many cytokine receptors including receptors for IL-1β, IL-2, IL-6, IL-17, IL-18, IL-33, type I IFNs, type III IFNs, GM-CSF, M-CSF, and TGF-β Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I- like receptors, and C-type lectin receptors
TRAF6 was crucial for IL-25R-mediated NFkB activation and IL-25 induced gene expression of IL-6, TGFβ, G-CSF, TARC (Thymus and activation-Regulated chemokine) but not activation of mitogen-activated protein kinases (MAPKs) pathway [40]. These studies demonstrated that IL-25 induced activation of extracellular signal-regulated kinase (ERK), Jun N-terminal protein kinase (JNK), P38 was intact in the absence of TRAF6, suggesting that MAPK downstream pathway is independent from TRAF6 unlike IL-25R-mediated NFkB activation and gene expression

Summary

Introduction

University of New Jersey, United States Bin Li, Shanghai Jiao Tong University School of Medicine, China. Tumor necrosis factor receptor (TNFR)-associated factors or (TRAFs) are important mediators of Interleukin-17 (IL-17) cytokine signaling and contribute to driving tissue responses that are crucial for protective immunity but are often implicated in immunopathology. E3 ubiquitin ligase activity of the RING domain has been shown to be required for TRAF-dependent activation of nuclear factor kappa-B NFκB1 and NFκB2, mitogen-activated protein kinases (MAPKs); extracellular signal-regulated kinase (ERK), P38, and Jun N-terminal protein kinase (JNK) as well as interferon regulatory factors/IRFs and downstream gene expression [7].

Results

Conclusion