T cell development involves TRAF3IP3-mediated ERK signaling in the Golgi

Zou, Qiang; Jin, Jin; Xiao, Yichuan; Hu, Hongbo; Zhou, Xiaofei; Jie, Zuliang; Xie, Xiaoping; Li, Kairong; Cheng, Xuhong; Sun, Shao Cong

doi:10.1084/jem.20150110

Cited by 31 publications

(37 citation statements)

References 36 publications

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“…Our results showed that the TM domain of TRAF3IP3 was critical for its interaction with MAVS ( Fig 1F). Additionally, we examined a panel of human cells and observed a broad spectrum of endogenous TRAF3IP3 expression ( Fig 1G), in contrast to previous reports indicating that mouse TRAF3IP3 expression is limited to immune organs and tissues (Zou et al, 2015).…”

Section: Traf3ip3 Binds To Multimerized and Active Mavs-region IIIcontrasting

confidence: 78%

“…Having established that TRAF3IP3 mediates the recruitment of TRAF3 to MAVS for IFN induction, we next investigated how TRAF3IP3 might regulate antiviral signaling on the subcellular level. A previous study has shown that TRAF3IP3 mediates MEK‐BRAF interaction to facilitate ERK signaling at Golgi apparatus (Zou et al , ). The interaction with MAVS, however, suggests that TRAF3IP3 can localize to the mitochondrion because MAVS is a mitochondrial outer membrane protein.…”

Section: Resultsmentioning

confidence: 99%

“…A previous study has shown that TRAF3IP3 mediates MEK-BRAF interaction to facilitate ERK signaling at Golgi apparatus (Zou et al, 2015). The interaction with MAVS, however, suggests that TRAF3IP3 can localize to the mitochondrion because MAVS is a mitochondrial outer membrane protein.…”

Section: Traf3ip3 Accumulates On the Mitochondria After Virus Infectionmentioning

confidence: 95%

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TRAF 3 IP 3 mediates the recruitment of TRAF 3 to MAVS for antiviral innate immunity

Zhu

Zhang

et al. 2019

The EMBO Journal

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RIG‐I‐MAVS antiviral signaling represents an important pathway to stimulate interferon production and confer innate immunity to the host. Upon binding to viral RNA and Riplet‐mediated polyubiquitination, RIG‐I promotes prion‐like aggregation and activation of MAVS. MAVS subsequently induces interferon production by activating two signaling pathways mediated by TBK1‐IRF3 and IKK‐NF‐κB respectively. However, the mechanism underlying the activation of MAVS downstream pathways remains elusive. Here, we demonstrated that activation of TBK1‐IRF3 by MAVS‐Region III depends on its multimerization state and identified TRAF3IP3 as a critical regulator for the downstream signaling. In response to virus infection, TRAF3IP3 is accumulated on mitochondria and thereby facilitates the recruitment of TRAF3 to MAVS for TBK1‐IRF3 activation. Traf3ip3‐deficient mice demonstrated a severely compromised potential to induce interferon production and were vulnerable to RNA virus infection. Our findings uncover that TRAF3IP3 is an important regulator for RIG‐I‐MAVS signaling, which bridges MAVS and TRAF3 for an effective antiviral innate immune response.

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Section: Traf3ip3 Binds To Multimerized and Active Mavs-region IIIcontrasting

confidence: 78%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

TRAF 3 IP 3 mediates the recruitment of TRAF 3 to MAVS for antiviral innate immunity

Zhu

Zhang

et al. 2019

The EMBO Journal

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“…More specifically, while testosterone exposure and subsequent androgen receptor activity can promote innate immune cell differentiation and development, testosterone also reduces activity of these cells (Gubbels Bupp and Jorgensen, 2018). As such, the hub genes of the immune related modules highlight broad suppression of innate immune signaling (quail yellow: SASH3 , SLAMF8 , TRAF3IP3 ; manakin dark turquoise: INPPL1 , CCL14 , CCL3L , ncRNA; (Beer et al, 2005; Veillette, 2010; Dauphinee et al, 2013; Sokol and Luster, 2015; Zou et al, 2015; Thomas et al, 2017; Wang et al, 2018). Similarly, testosterone exposure had substantial effects on the regulation of the adaptive immune system.…”

Section: Discussionmentioning

confidence: 99%

Developing a transcriptomic framework for testing testosterone-mediated handicap hypotheses

Newhouse

Vernasco

2019

Preprint

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13Sexually selected traits are hypothesized to be honest signals of individual quality due to the 14 costs associated with their development or expression. Testosterone, a sex steroid known to 15 influence the production of sexually selected traits, has been proposed to underlie the costs 16 associated with sexually selected traits via its immunosuppressive effects (i.e., the 17 Immunocompetence Handicap Hypothesis) or by influencing an individual's 18 exposure/susceptibility to oxidative stress (i.e., the Oxidation Handicap Hypothesis). Previous 19 work testing these hypotheses has primarily focused on physiological measurements of immunity 20 or oxidative stress, but little is known about the molecular pathways by which testosterone could 21 influence immunity and/or oxidative stress pathways. To measure the molecular consequences of 22 experimentally elevated testosterone, we used previously published RNA-seq data from studies 23 that measured the transcriptome of individuals treated with either a testosterone-filled or an 24 empty (i.e., control) implant. Two studies encompassing two species of bird and three tissue 25 types fit our selection criteria. We found strong support for the Immunocompetence Handicap 26 Hypothesis, but no support for the Oxidation Handicap Hypothesis. More specifically, 27 testosterone-treated individuals exhibited strong signatures of immunosuppression, 28 encompassing both cell-mediated and humoral immunity. Our results suggest that testosterone 29 enforces the honesty of sexually-selected traits by influencing an individual's 30 immunocompetence rather than their exposure or susceptibility to oxidative stress.31 32

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“…As we know there are three MAPK signalings arms of JNK, p38 MAPK and ERK, which we show here are activated in T cells from CIA rats at various degrees. All the three pathways are reported to be involved in medicating T cell migration25. ERK1/2 are important downstream molecules of TCR signaling, moreover, GRK2 per se is a scaffold protein for the activation of ERK pathway26.…”

Section: Discussionmentioning

confidence: 99%

Paroxetine alleviates T lymphocyte activation and infiltration to joints of collagen-induced arthritis

Wang

et al. 2017

Sci Rep

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T cell infiltration to synovial tissue is an early pathogenic mechanism of rheumatoid arthritis (RA). In the present work, we reveal that G protein coupled receptor kinase 2 (GRK2) is abundantly expressed in T cells of collagen-induced arthritis (CIA). A GRK2 inhibitor, paroxetine protects the joints from inflammation and destruction, primarily through inhibition of both CD4+ helper T (Th) cell and CD8+ cytotoxic T (Tc) cell migration to synovial tissue. Meanwhile, paroxetine restores the balance of Th/Tc, effector Th (Theff)/ naïve Th (Thnaive) and effector Tc (Tceff)/ naïve Tc (Tcnaive) to equilibrium by elevating the frequency of Thnaive, Tcnaive and regulatory Th cells; reducing the increased Theff, activated Th and Tceff, having a similar effect as methotrexate (MTX). In addition, both serum and synovial IL-1β, TNF-α and CX3CL1 expression was effectively inhibited in treated rats. In vitro assay confirmed that paroxetine inhibits CX3CL1-induced T cell migration through blocking the activity of GRK2. Among three MAPK families, paroxetine was found to be able to decrease the phosphorylation of ERK. This study elucidates that paroxetine attenuates the symptoms of CIA rats due to its inhibitory effect on T cell activation and infiltration to synovial tissue via suppression of ERK pathway.

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T cell development involves TRAF3IP3-mediated ERK signaling in the Golgi

Abstract: Zou et al. identify a Golgi-associated factor, TRAF3-interacting protein 3 (TRAF3IP3), as a crucial mediator of thymocyte development regulating TCR-stimulated ERK signaling in the Golgi.

Cited by 31 publications

References 36 publications

TRAF 3 IP 3 mediates the recruitment of TRAF 3 to MAVS for antiviral innate immunity

TRAF 3 IP 3 mediates the recruitment of TRAF 3 to MAVS for antiviral innate immunity

Developing a transcriptomic framework for testing testosterone-mediated handicap hypotheses

Paroxetine alleviates T lymphocyte activation and infiltration to joints of collagen-induced arthritis

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