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Cellular & Molecular Immunology

Dang Wu, Pin Wu, Fuming Qiu, Qichun Wei, Jian Huang
γδT cells are a conserved population of innate lymphocytes with diverse structural and functional heterogeneity that participate in various immune responses during tumor progression. γδT cells perform potent immunosurveillance by exerting direct cytotoxicity, strong cytokine production and indirect antitumor immune responses. However, certain γδT-cell subsets also contribute to tumor progression by facilitating cancer-related inflammation and immunosuppression. Here, we review recent observations regarding the antitumor and protumor roles of major structural and functional subsets of human γδT cells, describing how these subsets are activated and polarized, and how these events relate to subsequent function in tumor immunity...
November 28, 2016: Cellular & Molecular Immunology
Yifan Zhou, Jianfeng Wu, Chunxiao Liu, Xueheng Guo, Xinyi Zhu, Yuan Yao, Yuhao Jiao, Peng He, Jiahuai Han, Li Wu
The role of the p38 signaling pathway in the innate and adaptive immune responses has been well documented, especially in inflammatory cytokine production by dendritic cells (DCs). However, whether the p38 signaling pathway affects the important antigen (Ag) presentation function of DCs remains largely unknown. In this study, we reported that the deletion of p38α resulted in an impaired cross-presentation ability of CD8(+) conventional DCs (cDCs) and a reduction in the direct presentation ability of CD8(-) cDCs ex vivo...
November 21, 2016: Cellular & Molecular Immunology
Xiaoyu Zhang, Juliang Qin, Junyan Zou, Zhangsheng Lv, Binghe Tan, Jueping Shi, Yihan Zhao, Hua Ren, Mingyao Liu, Min Qian, Bing Du
As the most prominent clinical drug targets for the inhibition of platelet aggregation, P2Y12 and P2Y13 have been found to be highly expressed in both platelets and macrophages. However, the roles and function of P2Y12/13 in the regulation of macrophage-mediated innate immune responses remain unclear. Here, we demonstrate that adenosine 5'-diphosphate (ADP), the endogenous ligand of P2Y1, P2Y12 and P2Y13, was released both in E. coli-infected mice and from macrophages treated with either lipopolysaccharide (LPS) or Pam3CSK4...
November 21, 2016: Cellular & Molecular Immunology
Hong Bai, Xiaoling Gao, Lei Zhao, Ying Peng, Jie Yang, Sai Qiao, Huili Zhao, Shuhe Wang, YiJun Fan, Antony George Joyee, Zhi Yao, Xi Yang
The role of IL-17A is important in protection against lung infection with Chlamydiae, an obligate intracellular bacterial pathogen. In this study, we explored the producers of IL-17A in chlamydial lung infection and specifically tested the role of major IL-17A producers in protective immunity. We found that γδT cells and Th17 cells are the major producers of IL-17A at the early and later stages of chlamydial infection, respectively. Depletion of γδT cells in vivo at the early postinfection (p.i.) stage, when most γδT cells produce IL-17A, failed to alter Th1 responses and bacterial clearance...
October 31, 2016: Cellular & Molecular Immunology
Yongxia Wu, Xue-Zhong Yu
No abstract text is available yet for this article.
October 31, 2016: Cellular & Molecular Immunology
Xiaonan Zhuang, Zijuan Chen, Chenxi He, Lin Wang, Ruixue Zhou, Dapeng Yan, Baoxue Ge
To successfully infect host cells and evade the host immune response, a type III secretion system (T3SS) is commonly used by enteric bacterial pathogens such as enteropathogenic Escherichia coli (EPEC). Recent findings have revealed that various effectors are injected into host cells through the T3SS and exert an inhibitory effect on inflammatory signaling pathways, subverting the immune responses to these pathogens. Here we review recent studies aimed at addressing the modulation of several important inflammatory signaling pathways modulated by EPEC effector proteins, such as the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, which provides insight into the unfinished work in this unexplored field and helps to identify novel positions in inflammatory signaling networks for EPEC effectors...
October 31, 2016: Cellular & Molecular Immunology
Yifeng Cai, Shoubao Ma, Yuejun Liu, Huanle Gong, Qiao Cheng, Bo Hu, Yan Wu, Xiao Yu, Chen Dong, Kai Sun, Depei Wu, Haiyan Liu
The role of IL-17 and IL-17-producing CD4(+) T cells in acute graft-versus-host disease (GVHD) has been controversial in recent mouse and human studies. We carried out studies in a murine acute GVHD model of fully major histocompatibility complex-mismatched myeloablative bone marrow transplantation. We showed that donor wild-type CD4(+) T cells exacerbated acute GVHD compared with IL-17(-/-) CD4(+) T cells, while IL-17 reduced the severity of acute GVHD. The augmentation of acute GVHD by transferred donor IL-17-producing CD4(+) T cells was associated with increased Th1 responses, while IL-17 decreased the percentages of Th1 cells in the GVHD target organs...
October 17, 2016: Cellular & Molecular Immunology
Yajuan Li, Yuelong Li, Xiaocong Cao, Xiangyu Jin, Tengchuan Jin
Pattern recognition receptors (PRRs) and their signaling pathways have essential roles in recognizing various components of pathogens as well as damaged cells and triggering inflammatory responses that eliminate invading microorganisms and damaged cells. The zebrafish relies heavily on these primary defense mechanisms against pathogens. Here, we review the major PRR signaling pathways in the zebrafish innate immune system and compare these signaling pathways in zebrafish and humans to reveal their evolutionary relationship and better understand their innate immune defense mechanisms...
October 10, 2016: Cellular & Molecular Immunology
Rita Diehl, Fabienne Ferrara, Claudia Müller, Antje Y Dreyer, Damian D McLeod, Stephan Fricke, Johannes Boltze
Almost every experimental treatment strategy using non-autologous cell, tissue or organ transplantation is tested in small and large animal models before clinical translation. Because these strategies require immunosuppression in most cases, immunosuppressive protocols are a key element in transplantation experiments. However, standard immunosuppressive protocols are often applied without detailed knowledge regarding their efficacy within the particular experimental setting and in the chosen model species. Optimization of such protocols is pertinent to the translation of experimental results to human patients and thus warrants further investigation...
October 10, 2016: Cellular & Molecular Immunology
Li-Dan Zhao, Di Liang, Xiang-Ni Wu, Yang Li, Jing-Wen Niu, Chen Zhou, Li Wang, Hua Chen, Wen-Jie Zheng, Yun-Yun Fei, Fu-Lin Tang, Yong-Zhe Li, Feng-Chun Zhang, Wei He, Xue-Tao Cao, Xuan Zhang
Aberrant expression of CXCR4 has been indicated to play a role in the pathogenesis of systemic lupus erythematosus (SLE), but the mechanism of CXCR4 dysregulation in SLE is unclear. This study is aimed to explore the clinical significance and possible mechanisms of abnormal CXCR4 expression on B cells from patients with untreated SLE. Expression of CXCR4 on peripheral B cells was determined by flow cytometry and western blotting. Freshly isolated B cells were cultured with exogenous interleukin 21(IL-21) in the presence or absence of CD40 ligand (CD40L) plus anti-IgM antibody (aIgM), and changes in CXCR4 expression were detected...
September 26, 2016: Cellular & Molecular Immunology
Jingjing Yan, Yuling Zhang, Shimeng Cheng, Bin Kang, Jinbiao Peng, Xiaodan Zhang, Meichun Yuan, Wenqi Chu, Wen Zhang, Jiayin Shen, Shuye Zhang
Interleukin-37 (IL-37) is an inhibitory member of the IL-1 family of cytokines. We previously found that balanced selection maintains common variations of the human IL37 gene. However, the functional consequences of this selection have yet to be validated. Here, using cells expressing exogenous IL-37 variants, including IL-37 Ref and IL-37 Var1 and Var2, we found that the three variants of IL-37 exhibited different immunoregulatory potencies in response to immune stimulation. The protein level of IL-37 Var2 was found to be significantly less than that of IL-37 Ref or Var1, despite the comparable mRNA levels of all three variants...
September 26, 2016: Cellular & Molecular Immunology
Laura Gómez-Jaramillo, Raquel Romero-García, Gema Jiménez-Gómez, Lisa Riegle, Ana Belén Ramos-Amaya, José Antonio Brieva, Marie Kelly-Worden, Antonio Campos-Caro
The production and secretion of antibodies by human plasma cells (PCs) are two essential processes of humoral immunity. The secretion process relies on a group of proteins known as soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs), which are located in the plasma membrane (t-SNAREs) and in the antibody-carrying vesicle membrane (v-SNARE), and mediate the fusion of both membranes. We have previously shown that SNAP23 and STX4 are the t-SNAREs responsible for antibody secretion. Here, using human PCs and antibody-secreting cell lines, we studied and characterized the expression and subcellular distribution of vesicle associated membrane protein (VAMP) isoforms, demonstrating that all isoforms (with the exception of VAMP1) are expressed by the referenced cells...
September 12, 2016: Cellular & Molecular Immunology
Juan Liu, Xuetao Cao
Innate sensing of pathogens by pattern-recognition receptors (PRRs) plays essential roles in the innate discrimination between self and non-self components, leading to the generation of innate immune defense and inflammatory responses. The initiation, activation and resolution of innate inflammatory response are mediated by a complex network of interactions among the numerous cellular and molecular components of immune and non-immune system. While a controlled and beneficial innate inflammatory response is critical for the elimination of pathogens and maintenance of tissue homeostasis, dysregulated or sustained inflammation leads to pathological conditions such as chronic infection, inflammatory autoimmune diseases...
November 2016: Cellular & Molecular Immunology
Joseph S Bednash, Rama K Mallampalli
Inflammasomes are multi-protein complexes that regulate the innate immune response by facilitating the release of inflammatory cytokines in response to pathogen exposure or cellular damage. Pro-inflammatory inflammasome signaling is vital to host defense and helps initiate the process of tissue repair following an insult to the host, but can be injurious, when excessive or chronic. As such, inflammasome activity is tightly regulated. Here we discuss one critical mechanism of inflammasome regulation, ubiquitination, that functions as a universal modulator of protein stability and trafficking...
November 2016: Cellular & Molecular Immunology
Aaron Ochel, Marcin Cebula, Mathias Riehn, Upneet Hillebrand, Christoph Lipps, Reinhold Schirmbeck, Hansjörg Hauser, Dagmar Wirth
Liver infections with hepatotropic viruses, such as hepatitis B virus and hepatitis C virus are accompanied by viral persistence and immune failure. CD8+ T cells are crucial mediators of the intrahepatic antiviral immune response. Chronic infections of the liver and other organs correlate with T-cell exhaustion. It was previously suggested that high antigen load could result in T-cell exhaustion. We aimed at elucidating the impact of different intrahepatic antigen loads on the quality of CD8+ T-cell-mediated immunity by employing an infection-free transgenic mouse model expressing ovalbumin (Ova) as the target antigen...
November 2016: Cellular & Molecular Immunology
Ankita Singh, Vishal Singh, Rajiv L Tiwari, Tulika Chandra, Ashutosh Kumar, Madhu Dikshit, Manoj K Barthwal
In monocytic cells, Toll-like receptor 4 (TLR4)- and TLR2-induced reactive oxygen species (ROS) cause oxidative stress and inflammatory response; however, the mechanism is not well understood. The present study investigated the role of interleukin-1 receptor-associated kinase (IRAK), extracellular signal-regulated kinase (ERK), p67phox and Nox-2 in TLR4- and TLR2-induced ROS generation during interleukin-1 beta (IL-1β) transcription, processing, and secretion. An IRAK1/4 inhibitor, U0126, PD98059, an NADPH oxidase inhibitor (diphenyleneiodonium (DPI)), and a free radical scavenger (N-acetyl cysteine (NAC))-attenuated TLR4 (lipopolysaccharide (LPS))- and TLR2 (Pam3csk4)-induced ROS generation and IL-1β production in THP-1 and primary human monocytes...
November 2016: Cellular & Molecular Immunology
Catherine Desrumaux, Stéphanie Lemaire-Ewing, Nicolas Ogier, Akadiri Yessoufou, Arlette Hammann, Anabelle Sequeira-Le Grand, Valérie Deckert, Jean-Paul Pais de Barros, Naïg Le Guern, Julien Guy, Naim A Khan, Laurent Lagrost
OBJECTIVE: Plasma phospholipid transfer protein (PLTP) is a key determinant of lipoprotein metabolism, and both animal and human studies converge to indicate that PLTP promotes atherogenesis and its thromboembolic complications. Moreover, it has recently been reported that PLTP modulates inflammation and immune responses. Although earlier studies from our group demonstrated that PLTP can modify macrophage activation, the implication of PLTP in the modulation of T-cell-mediated immune responses has never been investigated and was therefore addressed in the present study...
November 2016: Cellular & Molecular Immunology
Xiaofan Lu, Zhen Li, Qunhui Li, Yanmei Jiao, Yunxia Ji, Hongwei Zhang, Zhuoming Liu, Wei Li, Hao Wu
Preferential infection and depletion of gut-homing α4β7 CD4(+) T cells in the blood are observed in chronic HIV/SIV infection. The dynamic change in gut-homing α4β7 CD4(+) T cells and their functional subsets during the acute stages of HIV-1 infection are less documented. Therefore, we conducted a cohort study to investigate whether acute HIV-1 infection induced abnormalities in gut-homing α4β7 CD4(+) T cells and their functional subsets. We examined the frequency, absolute number, and functionality of gut-homing α4β7 CD4(+) T cells in 26 acute HIV-1-infected patients compared with 20 healthy individuals...
November 2016: Cellular & Molecular Immunology
Jeong-Min Lee, Young-Saeng Jang, Bo-Ra Jin, Sun-Jin Kim, Hyeon-Jin Kim, Bo-Eun Kwon, Hyun-Jeong Ko, Sung-Il Yoon, Geun-Shik Lee, Woan-Sub Kim, Goo-Young Seo, Pyeung-Hyeun Kim
Lactoferrin (LF) and retinoic acid (RA) are enriched in colostrum, milk, and mucosal tissues. We recently showed that LF-induced IgA class switching through binding to betaglycan (transforming growth factor-beta receptor III, TβRIII) and activation of canonical TGF-β signaling. We investigated the combined effect of LF and RA on the overall IgA response. An increase in IgA production by LF was further augmented by RA. This combination effect was also evident in Ig germ-line α (GLα) transcription and GLα promoter activity, indicating that LF in cooperation with RA increased IgA isotype switching...
November 2016: Cellular & Molecular Immunology
Wonyong Lee, Hyeong Su Kim, Song Yi Baek, Gap Ryol Lee
Recent studies have suggested that regulatory T (Treg) cells comprise a heterogeneous population that regulates various aspects of the immune response, and that Treg cells use the factors that are expressed in their target cells to regulate them. We searched for factors that regulate Th1 response in Treg cells using a meta-analysis. In the process, we discovered that transcription factor interferon regulatory factor 8 (IRF8) was selectively expressed in Treg and Th1 cells. IRF8-deficient Treg cells showed defective expression of CXCR3 and aberrant expression of the Il4 and Il17 genes...
November 2016: Cellular & Molecular Immunology
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