Weilin Chen

Publications (7)65.43 Total impact

• Article: Induction of Siglec-G by RNA Viruses Inhibits the Innate Immune Response by Promoting RIG-I Degradation.

  Weilin Chen, Chaofeng Han, Bin Xie, Xiang Hu, Qian Yu, Liyun Shi, Qingqing Wang, Dongling Li, Jianli Wang, Pan Zheng, Yang Liu, Xuetao Cao
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  ABSTRACT: RIG-I is a critical RNA virus sensor that serves to initiate antiviral innate immunity. However, posttranslational regulation of RIG-I signaling remains to be fully understood. We report here that RNA viruses, but not DNA viruses or bacteria, specifically upregulate lectin family member Siglecg expression in macrophages by RIG-I- or NF-κB-dependent mechanisms. Siglec-G-induced recruitment of SHP2 and the E3 ubiquitin ligase c-Cbl to RIG-I leads to RIG-I degradation via K48-linked ubiquitination at Lys813 by c-Cbl. By increasing type I interferon production, targeted inactivation of Siglecg protects mice against lethal RNA virus infection. Taken together, our data reveal a negative feedback loop of RIG-I signaling and identify a Siglec-G-mediated immune evasion pathway exploited by RNA viruses with implication in antiviral applications. These findings also provide insights into the functions and crosstalk of Siglec-G, a known adaptive response regulator, in innate immunity.
  Cell 01/2013; 152(3):467-78. · 32.40 Impact Factor
• Article: MicroRNA-92a negatively regulates TLR-triggered inflammatory response in macrophages by targeting MKK4.

  Lihua Lai, Yinjing Song, Yang Liu, Qingyun Chen, Quan Han, Weilin Chen, Ting Pan, Yuanyuan Zhang, Xuetao Cao, Qingqing Wang
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  ABSTRACT: Toll-like receptors (TLRs) play a critical role in the initiation of immune responses against invading pathogens. MicroRNAs have been shown to be important regulators of TLR signaling. In this study, we have found that the stimulation of multiple TLRs rapidly reduced the levels of microRNA-92a and some other members of the miRNA-92a family in macrophages. MiR-92a mimics significantly decreased, whereas miR-92a knockdown increased, the activation of the JNK/C-JUN pathway and the production of inflammatory cytokines in macrophages when stimulated with ligands for TLR4. Furthermore, mitogen-activated protein kinase kinase 4 (MKK4) a kinase that activates JNK/stress-activated protein kinase, was found to be directly targeted by miR-92a. Similar to the effects of the miR-92a mimics, knockdown of MKK4 inhibited the activation of JNK/C-JUN signaling and the production of TNF-α and IL-6. In conclusion, we have demonstrated that TLR-mediated miR-92a reduction feedback enhances TLR-triggered production of inflammatory cytokines in macrophages, thus outlining new mechanisms for fine-tuning the TLR-triggered inflammatory response.
  Journal of Biological Chemistry 01/2013; · 4.77 Impact Factor
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  Available from: pnas.org

  Article: Ras-related protein Rab10 facilitates TLR4 signaling by promoting replenishment of TLR4 onto the plasma membrane.

  Di Wang, Jun Lou, Chuan Ouyang, Weilin Chen, Yiqi Liu, Xinyuan Liu, Xuetao Cao, Jianli Wang, Linrong Lu
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  ABSTRACT: The Toll-like receptor (TLR)4 receptor complex, TLR4/MD-2, plays an important role in the inflammatory response against lipopolysaccharide, a ubiquitous membrane component in Gram-negative bacteria. Ligand recognition by TLR4 initiates multiple intracellular signaling pathways, leading to production of proinflammatory mediators and type I IFN. Ligand interaction also leads to internalization of the surface receptor complex into lysosomes, leading to the degradation of TLR4 and the termination of LPS response. However, surface level of TLR4 receptor complex is maintained via continuous replenishment of TLR4 from intracellular compartments like Golgi and endosomes. Here we show that continuous replenishment of TLR4 from Golgi to plasma membrane is regulated by the small GTPase Rab10, which is essential for optimal macrophage activation following LPS stimulation. Expression of Rab10 is inducible by LPS. Blockade of Rab10 function leads to decreased membrane TLR4 expression and diminished production of inflammatory cytokines and interferons upon LPS stimulation. These findings suggest that Rab10 expression provides a mechanism to refine TLR4 signaling by regulating the trafficking rate of TLR4 onto the plasma membrane. In addition, we show that altered Rab10 expression in macrophages influences disease severity in an in vivo model of LPS-induced acute lung injury, suggesting Rab10 as a possible therapeutic target for human acute respiratory distress syndrome (ARDS).
  Proceedings of the National Academy of Sciences 08/2010; 107(31):13806-11. · 9.68 Impact Factor
• Article: Efficient induction of antitumor T cell immunity by exosomes derived from heat-shocked lymphoma cells.

  Weilin Chen, Jianli Wang, Chuansen Shao, Shuxun Liu, Yizhi Yu, Qingqing Wang, Xuetao Cao
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  ABSTRACT: Exosomes secreted by tumor cells could serve as a promising immunotherapeutic tumor vaccine. Heat shock proteins (HSP) induced in tumor cells by heat shock are molecular chaperones with potent adjuvant activity in the induction of antigen-specific T cell responses. To improve exosome-based tumor vaccines, we have investigated the efficacy of exosomes derived from heat-shocked mouse B lymphoma cells (HS-Exo) in the induction of antitumor immune responses. We found that HS-Exo, compared with control exosomes derived from the same cells (Exo), contain more HSP60 and HSP90 and increased amounts of molecules involved in immunogenicity including MHC class I, MHC class II, CD40, CD86, RANTES and IL-1beta. Furthermore, HS-Exo induce both phenotypic and functional maturation of dendritic cells more efficiently. HS-Exo immunization activates T cell responses more potently. Importantly, HS-Exo induce dramatically increased antitumor immune responses compared to control exosomes from the same cells in prophylaxis and therapeutic in vivo lymphoma models. We further demonstrate that CD8(+) T cells are the predominant T cell subset responsible for the antitumor effect of HS-Exo and that CD4(+) T cells are necessary in the induction phase of tumor rejection in a prophylaxis model. These findings provide a novel strategy to improve the efficacy of exosome-based tumor vaccines.
  European Journal of Immunology 07/2006; 36(6):1598-607. · 5.10 Impact Factor
• Article: Heat shock up-regulates TLR9 expression in human B cells through activation of ERK and NF-kappaB signal pathways.

  Weilin Chen, Jianli Wang, Huazhang An, Jun Zhou, Lihuang Zhang, Xuetao Cao
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  ABSTRACT: Toll-like receptors (TLRs) play a critical role in innate immunity and TLR9 is essential for CpG ODN signaling. As "dangerous signal", heat shock may regulate immune response. However, little is known about TLRs expression and signaling after heat shock. In this study, we investigated regulation of TLR9 expression and function in human B cell line RPMI8226 by heat shock. We demonstrated that TLR9 expression was up-regulated remarkably following heat shock. Coincidently, CpG ODN stimulation significantly increased IL-6 production and up-regulated expressions of MHC I, MHC II and CD86 by heat-shocked B cells. Heat shock activated ERK and NF-kappaB signal pathways, and pretreatment of B cells with specific inhibitors of ERK or NF-kappaB signal pathways inhibited heat shock-induced up-regulation of TLR9 expression. These results demonstrated that heat shock promotes TLR9 expression and signaling through activation of ERK and NF-kappaB signal pathways in B cells, suggesting that heat shock might modulate host immune response by regulating TLR expression.
  Immunology Letters 05/2005; 98(1):153-9. · 2.53 Impact Factor
• Article: Fas ligation induces IL-1beta-dependent maturation and IL-1beta-independent survival of dendritic cells: different roles of ERK and NF-kappaB signaling pathways.

  Zhenhong Guo, Minghui Zhang, Huazhang An, Weilin Chen, Shuxun Liu, Jun Guo, Yizhi Yu, Xuetao Cao
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  ABSTRACT: The mechanisms that underpin the intriguing capacity of Fas ligation on dendritic cells (DCs) to induce maturation and activation, rather than apoptosis, remain unclear. In the present study we confirm that Fas signaling induces both phenotypic and functional maturation of murine DCs, and we demonstrate that phenotypic maturation is associated with phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, activation of caspase-1, and secretion of interleukin-beta (IL-1beta). Specific inhibition of ERK1/2 diminished Fas ligation-induced caspase-1 activation, IL-1beta secretion, and ensuing up-regulation of developmental markers, whereas treatment with neutralizing anti-IL-1beta antibody abrogated phenotypic and functional maturation, indicating that IL-1beta mediates Fas ligation-induced DC maturation in an autocrine manner. NF-kappaB activation was responsible for maintaining DC viability after Fas ligation. Inhibiting NF-kappaB did not affect either IL-1beta secretion or phenotypic maturation but rather sensitized DCs to Fas-mediated apoptosis. In conclusion, positive signals originating from Fas are transduced through at least 2 different intracellular pathways in DCs, promoting not only survival but also an increase in maturation that correlates with increased antigen-presentation capability.
  Blood 01/2004; 102(13):4441-7. · 9.90 Impact Factor
• Article: Player-spectator discrepancies on risk preference during decision making.

  Xiuyan Guo, Nan Zhao, Si Wang, Weilin Chen, Rong Gong, Baihua Xu, Zhiliang Yang
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  ABSTRACT: Risk preference during decision making depends not only on the potential risk and profits but also on the roles taken in the current task. Those who perform tasks are more risk-seeking than those who only watch. Given the prominent effect of experiencing the task, the player-spectator discrepancies are supposed to arise in the experiencing phase instead of the choosing phase. In the present study, the authors separated the experiencing role and the choosing role through a stylus maze task in which participants first performed in pairs-one as the player and the other as the spectator-and then chose from two rewarding options for themselves or their partners. The findings show that the experience as players induced a risk-seeking tendency in decision making, which suggests that it was the experiencing role, rather than the choosing role, that caused the difference of risk preference, at least for financially motivated groups and under similar task conditions.
  The Journal of General Psychology 137(2):210-24. · 1.04 Impact Factor