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Journal of Immunology: Official Journal of the American Association of Immunologists

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https://www.readbyqxmd.com/read/28100682/diet-derived-short-chain-fatty-acids-stimulate-intestinal-epithelial-cells-to-induce-mucosal-tolerogenic-dendritic-cells
#1
Gera Goverse, Rosalie Molenaar, Laurence Macia, Jian Tan, Martje N Erkelens, Tanja Konijn, Marlene Knippenberg, Emma C L Cook, Diana Hanekamp, Marc Veldhoen, Anita Hartog, Guus Roeselers, Charles R Mackay, Reina E Mebius
The gastrointestinal tract is continuously exposed to many environmental factors that influence intestinal epithelial cells and the underlying mucosal immune system. In this article, we demonstrate that dietary fiber and short chain fatty acids (SCFAs) induced the expression of the vitamin A-converting enzyme RALDH1 in intestinal epithelial cells in vivo and in vitro, respectively. Furthermore, our data showed that the expression levels of RALDH1 in small intestinal epithelial cells correlated with the activity of vitamin A-converting enzymes in mesenteric lymph node dendritic cells, along with increased numbers of intestinal regulatory T cells and a higher production of luminal IgA...
January 18, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28100681/lfa-1-activation-in-nk-cells-and-their-subsets-influence-of-receptors-maturation-and-cytokine-stimulation
#2
Doris Urlaub, Kristine Höfer, Martha-Lena Müller, Carsten Watzl
The integrin LFA-1 is essential for efficient activation and for cytotoxicity of NK cells because it initiates the assembly of the immunological synapse and mediates firm adhesion to the target. LFA-1 is also needed to polarize the cytotoxic machinery of the NK cell toward the target cell. The binding affinity and avidity of integrins can be regulated via inside-out signals from other receptors. In this article, we investigate the signals necessary to activate LFA-1 in human NK cells. Our data show that LFA-1 has a low ligand-binding activity in resting human NK cells, but it can be stimulated by triggering activating receptors, such as 2B4 or CD16, or by coactivation of different receptor combinations...
January 18, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28100680/th22-cells-form-a-distinct-th-lineage-from-th17-cells-in-vitro-with-unique-transcriptional-properties-and-tbet-dependent-th1-plasticity
#3
Maximilian W Plank, Gerard E Kaiko, Steven Maltby, Jessica Weaver, Hock L Tay, Wei Shen, Mark S Wilson, Scott K Durum, Paul S Foster
Th22 cells are a major source of IL-22 and have been found at sites of infection and in a range of inflammatory diseases. However, their molecular characteristics and functional roles remain largely unknown because of our inability to generate and isolate pure populations. We developed a novel Th22 differentiation assay and generated dual IL-22/IL-17A reporter mice to isolate and compare pure populations of cultured Th22 and Th17 cells. Il17a fate-mapping and transcriptional profiling provide evidence that these Th22 cells have never expressed IL-17A, suggesting that they are potentially a distinct cell lineage from Th17 cells under in vitro culture conditions...
January 18, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28100679/etv5-regulates-il-10-production-in-th-cells
#4
Byunghee Koh, Matthew M Hufford, Xin Sun, Mark H Kaplan
IL-10 is an immunoregulatory cytokine that has broad effects across the immune system. In Th cell subsets, Th2 cells produce considerable amounts of IL-10. The transcription factors that regulate IL-10 production in Th2 cells are still incompletely described. In this study, we demonstrate that the ETS family transcription factor ETS variant (Etv)5 regulates IL-10 production in Th2 cells. T cell-specific Etv5-deficient and littermate control mice demonstrated that IL-10 production and gene expression were significantly decreased in the absence of Etv5...
January 18, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28100678/modulation-of-naive-cd8-t-cell-response-features-by-ligand-density-affinity-and-continued-signaling-via-internalized-tcrs
#5
Renu Balyan, Rupali Gund, Chitra Ebenezer, Jasneet Kaur Khalsa, Divya Anna Verghese, Thyagarajan Krishnamurthy, Anna George, Vineeta Bal, Satyajit Rath, Ashutosh Chaudhry
T cell response magnitudes increase with increasing antigenic dosage. However, it is unclear whether ligand density only modulates the proportions of responding ligand-specific T cells or also alters responses at the single cell level. Using brief (3 h) exposure of TCR-transgenic mouse CD8 T cells in vitro to varying densities of cognate peptide-MHC ligand followed by ligand-free culture in IL-2, we found that ligand density determined the frequencies of responding cells but not the expression levels of the early activation marker molecule, CD69...
January 18, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28093528/a-b-cell-epitope-peptide-derived-from-the-major-grass-pollen-allergen-phl-p-1-boosts-allergen-specific-secondary-antibody-responses-without-allergen-specific-t-cell-help
#6
Meena Narayanan, Raphaela Freidl, Margarete Focke-Tejkl, Ulrike Baranyi, Thomas Wekerle, Rudolf Valenta, Birgit Linhart
More than 40% of allergic patients suffer from grass pollen allergy. Phl p 1, the major timothy grass pollen allergen, belongs to the cross-reactive group 1 grass pollen allergens that are thought to initiate allergic sensitization to grass pollen. Repeated allergen encounter boosts allergen-specific IgE production and enhances clinical sensitivity in patients. To investigate immunological mechanisms underlying the boosting of allergen-specific secondary IgE Ab responses and the allergen epitopes involved, a murine model for Phl p 1 was established...
January 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28093527/human-cystic-fibrosis-macrophages-have-defective-calcium-dependent-protein-kinase-c-activation-of-the-nadph-oxidase-an-effect-augmented-by-burkholderia-cenocepacia
#7
Kaivon Assani, Chandra L Shrestha, Frank Robledo-Avila, Murugesan V Rajaram, Santiago Partida-Sanchez, Larry S Schlesinger, Benjamin T Kopp
Macrophage intracellular pathogen killing is defective in cystic fibrosis (CF), despite abundant production of reactive oxygen species (ROS) in lung tissue. Burkholderia species can cause serious infection in CF and themselves affect key oxidase components in murine non-CF cells. However, it is unknown whether human CF macrophages have an independent defect in the oxidative burst and whether Burkholderia contributes to this defect in terms of assembly of the NADPH oxidase complex and subsequent ROS production...
January 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28093526/cathepsin-k-deficiency-ameliorates-systemic-lupus-erythematosus-like-manifestations-in-faslpr-mice
#8
Yi Zhou, Huimei Chen, Li Liu, Xueqing Yu, Galina K Sukhova, Min Yang, Vasileios C Kyttaris, Isaac E Stillman, Bruce Gelb, Peter Libby, George C Tsokos, Guo-Ping Shi
Cysteinyl cathepsin K (CatK) is expressed in osteoclasts to mediate bone resorption, but is also inducible under inflammatory conditions. Fas(lpr) mice on a C57BL/6 background develop spontaneous systemic lupus erythematosus-like manifestations. Although normal mouse kidneys expressed negligible CatK, those from Fas(lpr) mice showed elevated CatK expression in the glomeruli and tubulointerstitial space. Fas(lpr) mice also showed elevated serum CatK levels. CatK deficiency in Fas(lpr) mice reduced all tested kidney pathologies, including glomerulus and tubulointerstitial scores, glomerulus complement C3 and IgG deposition, chemokine expression and macrophage infiltration, and serum autoantibodies...
January 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28093525/mafb-determines-human-macrophage-anti-inflammatory-polarization-relevance-for-the-pathogenic-mechanisms-operating-in-multicentric-carpotarsal-osteolysis
#9
Víctor D Cuevas, Laura Anta, Rafael Samaniego, Emmanuel Orta-Zavalza, Juan Vladimir de la Rosa, Geneviève Baujat, Ángeles Domínguez-Soto, Paloma Sánchez-Mateos, María M Escribese, Antonio Castrillo, Valérie Cormier-Daire, Miguel A Vega, Ángel L Corbí
Macrophage phenotypic and functional heterogeneity derives from tissue-specific transcriptional signatures shaped by the local microenvironment. Most studies addressing the molecular basis for macrophage heterogeneity have focused on murine cells, whereas the factors controlling the functional specialization of human macrophages are less known. M-CSF drives the generation of human monocyte-derived macrophages with a potent anti-inflammatory activity upon stimulation. We now report that knockdown of MAFB impairs the acquisition of the anti-inflammatory profile of human macrophages, identify the MAFB-dependent gene signature in human macrophages and illustrate the coexpression of MAFB and MAFB-target genes in CD163(+) tissue-resident and tumor-associated macrophages...
January 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28093524/age-associated-b-cells-express-a-diverse-repertoire-of-vh-and-v%C3%AE%C2%BA-genes-with-somatic-hypermutation
#10
Lisa M Russell Knode, Martin S Naradikian, Arpita Myles, Jean L Scholz, Yi Hao, Danya Liu, Mandy L Ford, John W Tobias, Michael P Cancro, Patricia J Gearhart
The origin and nature of age-associated B cells (ABCs) in mice are poorly understood. In this article, we show that their emergence required MHC class II and CD40/CD40L interactions. Young donor B cells were adoptively transferred into congenic recipients and allowed to remain for 1 mo in the absence of external Ag. B cells expressing the T-bet transcription factor, a marker for ABCs, were generated after multiple cell divisions from C57BL/6 donors but not from MHC class II- or CD40-deficient donors. Furthermore, old CD154 (CD40L)-deficient mice did not accrue ABCs, confirming that they arise primarily through T-dependent interactions...
January 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28093523/cutting-edge-nanog-activates-autophagy-under-hypoxic-stress-by-binding-to-bnip3l-promoter
#11
Meriem Hasmim, Bassam Janji, Mehdi Khaled, Muhammad Zaeem Noman, Fawzia Louache, Didier Bordereaux, Abdou Abderamane, Veronique Baud, Fathia Mami-Chouaib, Salem Chouaib
Hypoxia upregulates the core pluripotency factors NANOG, SOX2, and OCT4, associated with tumor aggressiveness and resistance to conventional anticancer treatments. We have previously reported that hypoxia-induced NANOG contributed in vitro to tumor cell resistance to autologous-specific CTL and in vivo to the in situ recruitment of immune-suppressive cells. In this study, we investigated the mechanisms underlying NANOG-mediated tumor cell resistance to specific lysis under hypoxia. We demonstrated the tumor-promoting effect of hypoxia on tumor initiation into immunodeficient mice using human non-small lung carcinoma cells...
January 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28093522/cutting-edge-human-cd49e-nk-cells-are-tissue-resident-in-the-liver
#12
Han Xian Aw Yeang, Sytse J Piersma, Yiing Lin, Liping Yang, Olga N Malkova, Cathrine Miner, Alexander S Krupnick, William C Chapman, Wayne M Yokoyama
Most knowledge on NK cells is based on studies of what are now known as conventional NK cells in the mouse spleen or human peripheral blood. However, recent studies in mice indicate the presence of tissue-resident NK cells in certain organs, such as the liver, that display different markers and transcription factor dependencies as compared with conventional NK cells. In this study, we provide evidence from cytometry by time-of-flight analysis and humanized mice indicating that human CD49e(-) NK cells are tissue resident in the liver...
January 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28093521/oncostatin-m-suppresses-activation-of-il-17-th17-via-socs3-regulation-in-cd4-t-cells
#13
Hye-Jin Son, Seung Hoon Lee, Seon-Yeong Lee, Eun-Kyung Kim, Eun-Ji Yang, Jae-Kyung Kim, Hyeon-Beom Seo, Sung-Hwan Park, Mi-La Cho
Oncostatin M (OSM) is a pleiotropic cytokine and a member of the IL-6 family. It has both proinflammatory and anti-inflammatory functions and is involved in the activation of STAT3 and STAT5. Rheumatoid arthritis is an autoimmune disease that causes chronic and excessive inflammation. Rheumatoid arthritis can lead to induction of Th17 cells, which express IL-17. The aim of this study was to measure the effects of OSM on the proliferation of regulatory T cells and Th17 cells from mice. IL-2 immune complex suppressed the development of collagen-induced arthritis in mice and altered the regulatory T/Th17 cell balance by increasing OSM expression...
January 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28087671/induction-and-differentiation-of-il-10-producing-regulatory-b-cells-from-healthy-blood-donors-and-rheumatoid-arthritis-patients
#14
Zsuzsanna Bankó, Judit Pozsgay, Dániel Szili, Mária Tóth, Tamás Gáti, György Nagy, Bernadette Rojkovich, Gabriella Sármay
The most important feature of B cells is the production of Abs upon activation; additionally, B cells produce pro- and anti-inflammatory cytokines in response to certain stimuli. IL-10-producing B cells represent a major subset of regulatory B cells (Bregs) that suppress autoimmune and inflammatory responses. B cells play a crucial role in the development and maintenance of the chronic inflammatory autoimmune disease rheumatoid arthritis (RA); however, controversial data are available on IL-10- producing Bregs in RA...
January 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28087670/plant-lectins-activate-the-nlrp3-inflammasome-to-promote-inflammatory-disorders
#15
Tao Gong, Xiaqiong Wang, Yanqing Yang, Yiqing Yan, Chenggong Yu, Rongbin Zhou, Wei Jiang
Plant-derived dietary lectins have been reported to be involved in the pathogenesis of several inflammatory diseases, including inflammatory bowel disease, diabetes, rheumatoid arthritis, and celiac disease, but little is known about the molecular mechanisms underlying lectin-induced inflammation. In this study, we showed that plant lectins can induce caspase-1 activation and IL-1β secretion via the NLRP3 inflammasome. Lectins were internalized and subsequently escaped from the lysosome and then translocated to the endoplasmic reticulum...
January 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28087669/the-role-of-the-p38-mnk-eif4e-signaling-axis-in-tnf-production-downstream-of-the-nod1-receptor
#16
Mikhail V Pashenkov, Lyudmila S Balyasova, Yulia A Dagil, Boris V Pinegin
Activation of nucleotide-binding oligomerization domain (NOD) 1 and NOD2 by muropeptides triggers a complex transcriptional program in innate immune cells. However, little is known about posttranscriptional regulation of NOD1- and NOD2-dependent responses. When stimulated with a prototypic NOD1 agonist, N-acetylglucosaminyl-N-acetylmuramyl-l-alanyl-d-isoglutamyl-meso-diaminopimelic acid (GM-triDAP), human monocyte-derived macrophages (MDM) produced an order of magnitude more TNF, IL-6, and pro-IL-1β than did monocyte-derived dendritic cells (MDDC), despite similar NOD1 expression, similar cytokine mRNA kinetics, and comparable responses to LPS...
January 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28087668/the-threshold-of-protection-from-liver-stage-malaria-relies-on-a-fine-balance-between-the-number-of-infected-hepatocytes-and-effector-cd8-t-cells-present-in-the-liver
#17
Alexandra J Spencer, Rhea J Longley, Anita Gola, Marta Ulaszewska, Teresa Lambe, Adrian V S Hill
Since the demonstration of sterile protection afforded by injection of irradiated sporozoites, CD8(+) T cells have been shown to play a significant role in protection from liver-stage malaria. This is, however, dependent on the presence of an extremely high number of circulating effector cells, thought to be necessary to scan, locate, and kill infected hepatocytes in the short time that parasites are present in the liver. We used an adoptive transfer model to elucidate the kinetics of the effector CD8(+) T cell response in the liver following Plasmodium berghei sporozoite challenge...
January 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28087667/prmt5-selective-inhibitors-suppress-inflammatory-t-cell-responses-and-experimental-autoimmune-encephalomyelitis
#18
Lindsay M Webb, Stephanie A Amici, Kyle A Jablonski, Himanshu Savardekar, Amanda R Panfil, Linsen Li, Wei Zhou, Kevin Peine, Vrajesh Karkhanis, Eric M Bachelder, Kristy M Ainslie, Patrick L Green, Chenglong Li, Robert A Baiocchi, Mireia Guerau-de-Arellano
In the autoimmune disease multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), expansion of pathogenic, myelin-specific Th1 cell populations drives active disease; selectively targeting this process may be the basis for a new therapeutic approach. Previous studies have hinted at a role for protein arginine methylation in immune responses, including T cell-mediated autoimmunity and EAE. However, a conclusive role for the protein arginine methyltransferase (PRMT) enzymes that catalyze these reactions has been lacking...
January 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28087666/dysregulation-of-b-cell-repertoire-formation-in-myasthenia-gravis-patients-revealed-through-deep-sequencing
#19
Jason A Vander Heiden, Panos Stathopoulos, Julian Q Zhou, Luan Chen, Tamara J Gilbert, Christopher R Bolen, Richard J Barohn, Mazen M Dimachkie, Emma Ciafaloni, Teresa J Broering, Francois Vigneault, Richard J Nowak, Steven H Kleinstein, Kevin C O'Connor
Myasthenia gravis (MG) is a prototypical B cell-mediated autoimmune disease affecting 20-50 people per 100,000. The majority of patients fall into two clinically distinguishable types based on whether they produce autoantibodies targeting the acetylcholine receptor (AChR-MG) or muscle specific kinase (MuSK-MG). The autoantibodies are pathogenic, but whether their generation is associated with broader defects in the B cell repertoire is unknown. To address this question, we performed deep sequencing of the BCR repertoire of AChR-MG, MuSK-MG, and healthy subjects to generate ∼518,000 unique VH and VL sequences from sorted naive and memory B cell populations...
January 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28087665/nkg2d-promotes-b1a-cell-development-and-protection-against-bacterial-infection
#20
Maja Lenartić, Vedrana Jelenčić, Biljana Zafirova, Mateja Ožanič, Valentina Marečić, Slaven Jurković, Veronika Sexl, Marina Šantić, Felix M Wensveen, Bojan Polić
NKG2D is a potent activating receptor that is expressed on cytotoxic immune cells such as CD8 T and NK cells, where it promotes cytotoxicity after binding stress ligands on infected or transformed cells. On NK cell precursors NKG2D modulates proliferation and maturation. Previously, we observed that NKG2D deficiency affects peripheral B cell numbers. In this study, we show that NKG2D regulates B1a cell development and function. We find that mice deficient for NKG2D have a strong reduction of B1a cell numbers...
January 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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