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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
Alexandra C Bolognese, Archna Sharma, Weng-Lang Yang, Jeffrey Nicastro, Gene F Coppa, Ping Wang
Cold-inducible RNA-binding protein (CIRP) is a novel inflammatory mediator that stimulates the release of proinflammatory cytokines from macrophages in sepsis. Given the immune dysregulation that characterizes sepsis, the effect of CIRP on other immune cells is an area of increasing interest that has not yet been studied. In the present study, we hypothesized that extracellular CIRP promotes activation of T lymphocytes in the spleen during sepsis. We observed that mice subjected to sepsis by cecal ligation and puncture showed significantly higher expression of the early activation markers CD69 and CD25 at 20 h on CD4(+) splenic T cells, and significantly higher CD69 expression on CD8(+) splenic T cells compared with sham-operated controls...
August 29, 2016: Cellular & Molecular Immunology
Damien Bertheloot, Eicke Latz
Our immune system is based on the close collaboration of the innate and adaptive immune systems for the rapid detection of any threats to the host. Recognition of pathogen-derived molecules is entrusted to specific germline-encoded signaling receptors. The same receptors have now also emerged as efficient detectors of misplaced or altered self-molecules that signal tissue damage and cell death following, for example, disruption of the blood supply and subsequent hypoxia. Many types of endogenous molecules have been shown to provoke such sterile inflammatory states when released from dying cells...
August 29, 2016: Cellular & Molecular Immunology
Derek Dc Ireland, Cecilia Tami, Joao Pedras-Vasconcelos, Daniela Verthelyi
Neonates are at increased risk of viral encephalopathies that can result in neurological dysfunction, seizures, permanent disability and even death. The neurological damage results from the combined effect of the virus and the immune response it elicits, thus finding tools to facilitate viral clearance from central nervous system (CNS) while minimizing neuron damage remains a critical challenge. Neonatal mice inoculated intraperitoneally with Tacaribe virus (TCRV) develop seizures, hindlimb paralysis and death within 15 days of inoculation...
August 29, 2016: Cellular & Molecular Immunology
Tsan Sam Xiao
No abstract text is available yet for this article.
August 22, 2016: Cellular & Molecular Immunology
Alicia M Holmgren, Cameron A McConkey, Sunny Shin
Originally described by the late evolutionary biologist Leigh Van Valen, the Red Queen hypothesis posits that the evolutionary arms race between hosts and their pathogens selects for discrete, genetically encoded events that lead to competitive advantages over the other species. Examples of immune evasion strategies are seen throughout the co-evolution of the mammalian immune system and pathogens, such as the enzymatic inactivation of nuclear factor-κB signaling or host translation by pathogen-encoded virulence factors...
August 22, 2016: Cellular & Molecular Immunology
Rojo A Ratsimandresy, Mohanalaxmi Indramohan, Andrea Dorfleutner, Christian Stehlik
Inflammasomes are important for maintaining intestinal homeostasis, and dysbiosis contributes to the pathology of inflammatory bowel disease (IBD) and increases the risk for colorectal cancer. Inflammasome defects contribute to chronic intestinal inflammation and increase the susceptibility to colitis in mice. However, the inflammasome sensor absent in melanoma 2 (AIM2) protects against colorectal cancer in an inflammasome-independent manner through DNA-dependent protein kinase and Akt pathways. Yet, the roles of the AIM2 inflammasome in IBD and the early phases of colorectal cancer remain ill-defined...
August 15, 2016: Cellular & Molecular Immunology
Soizic Garaud, Taher E Taher, Marjolaine Debant, Miguel Burgos, Sarra Melayah, Christian Berthou, Kaushal Parikh, Jacques-Olivier Pers, Damien Luque-Paz, Gilles Chiocchia, Maikel Peppelenbosch, David A Isenberg, Pierre Youinou, Olivier Mignen, Yves Renaudineau, Rizgar A Mageed
CD5 is constitutively expressed on T cells and a subset of mature normal and leukemic B cells in patients with chronic lymphocytic leukemia (CLL). Important functional properties are associated with CD5 expression in B cells, including signal transducer and activator of transcription 3 activation, IL-10 production and the promotion of B-lymphocyte survival and transformation. However, the pathway(s) by which CD5 influences the biology of B cells and its dependence on B-cell receptor (BCR) co-signaling remain unknown...
August 8, 2016: Cellular & Molecular Immunology
Longlong Luo, Shi Wang, Xiaoling Lang, Tingting Zhou, Jing Geng, Xinying Li, Chunxia Qiao, Jiannan Feng, Beifen Shen, Ming Lv, Yan Li
Currently, display-based methods are well established and widely used in antibody engineering for affinity maturation and structural stability improvement. We obtained a novel anti-human programmed death 1 (PD-1) antibody using computer-aided design and a mammalian cell display technology platform. We used computer-aided modeling and distance geometry methods to predict and assign the key residues that contributed to the binding of human PD-L1 to PD-1. Then, we analyzed the sequence of nivolumab (an anti-human PD-1 antibody, referred to as MIL75 in the article) to determine the template for antibody design and library construction...
August 8, 2016: Cellular & Molecular Immunology
Tao Yang, Linnan Zhu, Yanhua Zhai, Qingjie Zhao, Jianxia Peng, Hongbing Zhang, Zhongzhou Yang, Lianfeng Zhang, Wenjun Ding, Yong Zhao
The tuberous sclerosis complex 1 (TSC1) is a tumor suppressor that inhibits the mammalian target of rapamycin (mTOR), which serves as a key regulator of inflammatory responses after bacterial stimulation in monocytes, macrophages, and primary dendritic cells. Previous studies have shown that TSC1 knockout (KO) macrophages produced increased inflammatory responses including tumor necrosis factor-α (TNF-α) and IL-12 to pro-inflammatory stimuli, but whether and how TSC1 regulates pro-IL-1β expression remains unclear...
September 2016: Cellular & Molecular Immunology
Kylie Su Mei Yong, Choong Tat Keng, Shu Qi Tan, Eva Loh, Kenneth Te Chang, Thiam Chye Tan, Wanjin Hong, Qingfeng Chen
We have recently discovered a unique CD34(lo)CD133(lo) cell population in the human fetal liver (FL) that gives rise to cells in the hepatic lineage. In this study, we further characterized the biological functions of FL CD34(lo)CD133(lo) cells. Our findings show that these CD34(lo)CD133(lo) cells express markers of both endodermal and mesodermal lineages and have the capability to differentiate into hepatocyte and mesenchymal lineage cells by ex vivo differentiation assays. Furthermore, we show that CD34(lo)CD133(lo) cells express growth factors that are important for human hematopoietic stem cell (HSC) expansion: stem cell factor (SCF), insulin-like growth factor 2 (IGF2), C-X-C motif chemokine 12 (CXCL12), and factors in the angiopoietin-like protein family...
September 2016: Cellular & Molecular Immunology
Xueying Zhang, Zhenjie Ye, Yujun Pei, Guihua Qiu, Qingyang Wang, Yunlu Xu, Beifen Shen, Jiyan Zhang
Type I interferons such as interferon-beta (IFN-β) play essential roles in the host innate immune response to herpes simplex virus type I (HSV-1) infection. The transcription of type I interferon genes is controlled by nuclear factor-κB (NF-κB) and interferon regulatory factor (IRF) family members including IRF3. NF-κB activation depends on the phosphorylation of inhibitor of κB (IκB), which triggers its ubiqitination and degradation. It has been reported that neddylation inhibition by a pharmacological agent MLN4924 potently suppresses lipopolysaccharide (LPS)-induced proinflammatory cytokine production with the accumulation of phosphorylated IκBα...
September 2016: Cellular & Molecular Immunology
Zhi-Qing Hu
No abstract text is available yet for this article.
September 2016: Cellular & Molecular Immunology
Jie Li, Qi-Yao Chai, Cui Hua Liu
The ubiquitin system comprises enzymes that are responsible for ubiquitination and deubiquitination, as well as ubiquitin receptors that are capable of recognizing and deciphering the ubiquitin code, which act in coordination to regulate almost all host cellular processes, including host-pathogen interactions. In response to pathogen infection, the host innate immune system launches an array of distinct antimicrobial activities encompassing inflammatory signaling, phagosomal maturation, autophagy and apoptosis, all of which are fine-tuned by the ubiquitin system to eradicate the invading pathogens and to reduce concomitant host damage...
September 2016: Cellular & Molecular Immunology
P A Reyfman, E T Bartom, B D Singer
No abstract text is available yet for this article.
September 2016: Cellular & Molecular Immunology
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