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

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https://www.readbyqxmd.com/read/28931604/sublethal-total-body-irradiation-causes-long-term-deficits-in-thymus-function-by-reducing-lymphoid-progenitors
#1
Shiyun Xiao, Ivo D Shterev, Wen Zhang, Lauren Young, Jae-Hung Shieh, Malcolm Moore, Marcel van den Brink, Gregory D Sempowski, Nancy R Manley
Total body irradiation (TBI) damages hematopoietic cells in the bone marrow and thymus; however, the long-term effects of irradiation with aging remain unclear. In this study, we found that the impact of radiation on thymopoiesis in mice varied by sex and dose but, overall, thymopoiesis remained suppressed for ≥12 mo after a single exposure. Male and female mice showed a long-term dose-dependent reduction in thymic cKit(+) lymphoid progenitors that was maintained throughout life. Damage to hematopoietic stem cells (HSCs) in the bone marrow was dose dependent, with as little as 0...
September 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28931603/the-pyhin-protein-p205-regulates-the-inflammasome-by-controlling-asc-expression
#2
Sreya Ghosh, Christina Wallerath, Sergio Covarrubias, Veit Hornung, Susan Carpenter, Katherine A Fitzgerald
Members of the IFN-inducible PYHIN protein family, such as absent in melanoma-2 and IFN-γ-inducible protein (IFI)16, bind dsDNA and form caspase-1-activating inflammasomes that are important in immunity to cytosolic bacteria, DNA viruses, or HIV. IFI16 has also been shown to regulate transcription of type I IFNs during HSV infection. The role of other members of the PYHIN protein family in the regulation of immune responses is much less clear. In this study, we identified an immune-regulatory function for a member of the murine PYHIN protein family, p205 (also called Ifi205)...
September 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28931602/an-anti-inflammatory-role-for-nlrp10-in-murine-cutaneous-leishmaniasis
#3
Gwendolyn M Clay, Diogo G Valadares, Joel W Graff, Tyler K Ulland, Richard E Davis, Breanna M Scorza, Bayan Sudan Zhanbolat, Yani Chen, Fayyaz S Sutterwala, Mary E Wilson
The role of the nucleotide-binding domain and leucine-rich repeat containing receptor NLRP10 in disease is incompletely understood. Using three mouse strains lacking the gene encoding NLRP10, only one of which had a coincidental mutation in DOCK8, we documented a role for NLRP10 as a suppressor of the cutaneous inflammatory response to Leishmania major infection. There was no evidence that the enhanced local inflammation was due to enhanced inflammasome activity. NLRP10/DOCK8-deficient mice harbored lower parasite burdens at the cutaneous site of inoculation compared with wild-type controls, whereas NLRP10-deficient mice and controls had similar parasite loads, suggesting that DOCK8 promotes local growth of parasites in the skin, whereas NLRP10 does not...
September 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28924004/basic-fibroblast-growth-factor-2-is-a-determinant-of-cd4-t-cell-airway-smooth-muscle-cell-communication-through-membrane-conduits
#4
Soroor Farahnak, Toby K McGovern, Rachael Kim, Michael O'Sullivan, Brian Chen, Minhyoung Lee, Haruka Yoshie, Anna Wang, Joyce Jang, Saba Al Heialy, Anne-Marie Lauzon, James G Martin
Activated CD4 T cells connect to airway smooth muscle cells (ASMCs) in vitro via lymphocyte-derived membrane conduits (LMCs) structurally similar to membrane nanotubes with unknown intercellular signals triggering their formation. We examined the structure and function of CD4 T cell-derived LMCs, and we established a role for ASMC-derived basic fibroblast growth factor 2 (FGF2b) and FGF receptor (FGFR)1 in LMC formation. Blocking FGF2b's synthesis and FGFR1 function reduced LMC formation. Mitochondrial flux from ASMCs to T cells was partially FGF2b and FGFR1 dependent...
September 18, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28924003/learning-the-high-dimensional-immunogenomic-features-that-predict-public-and-private-antibody-repertoires
#5
Victor Greiff, Cédric R Weber, Johannes Palme, Ulrich Bodenhofer, Enkelejda Miho, Ulrike Menzel, Sai T Reddy
Recent studies have revealed that immune repertoires contain a substantial fraction of public clones, which may be defined as Ab or TCR clonal sequences shared across individuals. It has remained unclear whether public clones possess predictable sequence features that differentiate them from private clones, which are believed to be generated largely stochastically. This knowledge gap represents a lack of insight into the shaping of immune repertoire diversity. Leveraging a machine learning approach capable of capturing the high-dimensional compositional information of each clonal sequence (defined by CDR3), we detected predictive public clone and private clone-specific immunogenomic differences concentrated in CDR3's N1-D-N2 region, which allowed the prediction of public and private status with 80% accuracy in humans and mice...
September 18, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28916524/new-methods-to-analyze-b-cell-immune-responses-to-thymus-dependent-antigen-sheep-red-blood-cells
#6
Ellen J McAllister, John R Apgar, Charlotte R Leung, Robert C Rickert, Julia Jellusova
B cells contribute critically to an effective immune response by producing Ag-specific Abs. During the immune response to so-called "thymus-dependent Ags," activated B cells seek T cell help and form germinal centers. In contrast, thymus-independent Ags generally do not induce germinal center formation. In the germinal center, B cells undergo somatic hypermutation, affinity-based clonal expansion, and differentiation to produce plasma cells and memory B cells. Valuable insight into these processes has been gained by using model hapten-carrier complexes or SRBCs...
September 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28916523/cutting-edge-a-critical-role-of-lesional-t-follicular-helper-cells-in-the-pathogenesis-of-igg4-related-disease
#7
Ryuta Kamekura, Kenichi Takano, Motohisa Yamamoto, Koji Kawata, Katsunori Shigehara, Sumito Jitsukawa, Tomonori Nagaya, Fumie Ito, Akinori Sato, Noriko Ogasawara, Chieko Tsubomatsu, Hiroki Takahashi, Hiroshi Nakase, Tetsuo Himi, Shingo Ichimiya
IgG4-related disease (IgG4-RD) is a newly recognized systemic chronic fibroinflammatory disease. However, the pathogenesis of IgG4-RD remains unknown. To determine the pathophysiologic features of IgG4-RD, we examined T follicular helper (Tfh) cells in lesions and blood from patients with IgG4-RD. Patients with IgG4-related dacryoadenitis and sialadenitis (IgG4-DS) showed increased infiltration of Tfh cells highly expressing programmed death 1 and ICOS in submandibular glands. Tfh cells from IgG4-DS submandibular glands had higher expression of B cell lymphoma 6 and a greater capacity to help B cells produce IgG4 than did tonsillar Tfh cells...
September 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28916522/viral-infection-sensitizes-human-fetal-membranes-to-bacterial-lipopolysaccharide-by-mertk-inhibition-and-inflammasome-activation
#8
Sarah N Cross, Julie A Potter, Paulomi Aldo, Ja Young Kwon, Mary Pitruzzello, Mancy Tong, Seth Guller, Carla V Rothlin, Gil Mor, Vikki M Abrahams
Chorioamnionitis, premature rupture of fetal membranes (FMs), and subsequent preterm birth are associated with local infection and inflammation, particularly IL-1β production. Although bacterial infections are commonly identified, other microorganisms may play a role in the pathogenesis. Because viral pandemics, such as influenza, Ebola, and Zika, are becoming more common, and pregnant women are at increased risk for associated complications, this study evaluated the impact that viral infection had on human FM innate immune responses...
September 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28904129/t-cells-regulate-peripheral-naive-mature-b-cell-survival-by-cell-cell-contact-mediated-through-slamf6-and-sap
#9
Lihi Radomir, Sivan Cohen, Matthias P Kramer, Eszter Bakos, Hadas Lewinsky, Avital Barak, Ziv Porat, Richard Bucala, Polina Stepensky, Shirly Becker-Herman, Idit Shachar
The control of lymphoid homeostasis is the result of a very fine balance between lymphocyte production, proliferation, and apoptosis. In this study, we focused on the role of T cells in the maintenance/survival of the mature naive peripheral B cell population. We show that naive B and T cells interact via the signaling lymphocyte activation molecule (SLAM) family receptor, SLAMF6. This interaction induces cell type-specific signals in both cell types, mediated by the SLAM-associated protein (SAP) family of adaptors...
September 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28904128/integration-of-kinase-and-calcium-signaling-at-the-level-of-chromatin-underlies-inducible-gene-activation-in-t-cells
#10
Ruth Brignall, Pierre Cauchy, Sarah L Bevington, Bethany Gorman, Angela O Pisco, James Bagnall, Christopher Boddington, William Rowe, Hazel England, Kevin Rich, Lorraine Schmidt, Nigel P Dyer, Mark A Travis, Sascha Ott, Dean A Jackson, Peter N Cockerill, Pawel Paszek
TCR signaling pathways cooperate to activate the inducible transcription factors NF-κB, NFAT, and AP-1. In this study, using the calcium ionophore ionomycin and/or PMA on Jurkat T cells, we show that the gene expression program associated with activation of TCR signaling is closely related to specific chromatin landscapes. We find that calcium and kinase signaling cooperate to induce chromatin remodeling at ∼2100 chromatin regions, which demonstrate enriched binding motifs for inducible factors and correlate with target gene expression...
September 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28904127/therapeutic-effects-of-monoclonal-antibody-against-dengue-virus-ns1-in-a-stat1-knockout-mouse-model-of-dengue-infection
#11
Shu-Wen Wan, Pei-Wei Chen, Chin-Yu Chen, Yen-Chung Lai, Ya-Ting Chu, Chia-Yi Hung, Han Lee, Hsuan Franziska Wu, Yung-Chun Chuang, Jessica Lin, Chih-Peng Chang, Shuying Wang, Ching-Chuan Liu, Tzong-Shiann Ho, Chiou-Feng Lin, Chien-Kuo Lee, Betty A Wu-Hsieh, Robert Anderson, Trai-Ming Yeh, Yee-Shin Lin
Dengue virus (DENV) is the causative agent of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome and is endemic to tropical and subtropical regions of the world. Our previous studies showed the existence of epitopes in the C-terminal region of DENV nonstructural protein 1 (NS1) which are cross-reactive with host Ags and trigger anti-DENV NS1 Ab-mediated endothelial cell damage and platelet dysfunction. To circumvent these potentially harmful events, we replaced the C-terminal region of DENV NS1 with the corresponding region from Japanese encephalitis virus NS1 to create chimeric DJ NS1 protein...
September 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28904126/nlrp3-and-potassium-efflux-drive-rapid-il-1%C3%AE-release-from-primary-human-monocytes-during-toxoplasma-gondii-infection
#12
Lanny Gov, Christine A Schneider, Tatiane S Lima, William Pandori, Melissa B Lodoen
IL-1β is produced by myeloid cells and acts as a critical mediator of host defense during infection and injury. We found that the intracellular protozoan parasite Toxoplasma gondii induced an early IL-1β response (within 4 h) in primary human peripheral blood monocytes isolated from healthy donors. This process involved upregulation of IL-1β, IL-1RN (IL-1R antagonist), and NLRP3 transcripts, de novo protein synthesis, and the release of pro- and mature IL-1β from infected primary monocytes. The released pro-IL-1β was cleavable to mature bioactive IL-1β in the extracellular space by the protease caspase-1...
September 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28904125/enhancing-vaccine-efficacy-by-engineering-a-complex-synthetic-peptide-to-become-a-super-immunogen
#13
Therése Nordström, Manisha Pandey, Ainslie Calcutt, Jessica Powell, Zachary N Phillips, Grace Yeung, Ashwini K Giddam, Yun Shi, Thomas Haselhorst, Mark von Itzstein, Michael R Batzloff, Michael F Good
Peptides offer enormous promise as vaccines to prevent and protect against many infectious and noninfectious diseases. However, to date, limited vaccine efficacy has been reported and none have been licensed for human use. Innovative ways to enhance their immunogenicity are being tested, but rational sequence modification as a means to improve immune responsiveness has been neglected. Our objective was to establish a two-step generic protocol to modify defined amino acids of a helical peptide epitope to create a superior immunogen...
September 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28904124/cutting-edge-endogenous-ifn-%C3%AE-regulates-survival-and-development-of-transitional-b-cells
#14
Jennie A Hamilton, Qi Wu, PingAr Yang, Bao Luo, Shanrun Liu, Huixian Hong, Jun Li, Mark R Walter, Eleanor N Fish, Hui-Chen Hsu, John D Mountz
The transitional stage of B cell development is a formative stage in the spleen where autoreactive specificities are censored as B cells gain immune competence, but the intrinsic and extrinsic factors regulating survival of transitional stage 1 (T1) B cells are unknown. We report that B cell expression of IFN-β is required for optimal survival and TLR7 responses of transitional B cells in the spleen and was overexpressed in T1 B cells from BXD2 lupus-prone mice. Single-cell gene expression analysis of B6 Ifnb(+/+) versus B6 Ifnb(-⁄-) T1 B cells revealed heterogeneous expression of Ifnb in wild-type B cells and distinct gene expression patterns associated with endogenous IFN-β...
September 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28904123/unveiling-the-peptide-motifs-of-hla-c-and-hla-g-from-naturally-presented-peptides-and-generation-of-binding-prediction-matrices
#15
Moreno Di Marco, Heiko Schuster, Linus Backert, Michael Ghosh, Hans-Georg Rammensee, Stefan Stevanović
The classical HLA-C and the nonclassical HLA-E and HLA-G molecules play important roles both in the innate and adaptive immune system. Starting already during embryogenesis and continuing throughout our lives, these three Ags exert major functions in immune tolerance, defense against infections, and anticancer immune responses. Despite these important roles, identification and characterization of the peptides presented by these molecules has been lacking behind the more abundant HLA-A and HLA-B gene products...
September 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28893958/microbial-derived-butyrate-promotes-epithelial-barrier-function-through-il-10-receptor-dependent-repression-of-claudin-2
#16
Leon Zheng, Caleb J Kelly, Kayla D Battista, Rachel Schaefer, Jordi M Lanis, Erica E Alexeev, Ruth X Wang, Joseph C Onyiah, Douglas J Kominsky, Sean P Colgan
Commensal interactions between the enteric microbiota and distal intestine play important roles in regulating human health. Short-chain fatty acids (SCFAs), such as butyrate, produced through anaerobic microbial metabolism represent a major energy source for the host colonic epithelium and enhance epithelial barrier function through unclear mechanisms. Separate studies revealed that the epithelial anti-inflammatory IL-10 receptor α subunit (IL-10RA) is also important for barrier formation. Based on these findings, we examined if SCFAs promote epithelial barrier through IL-10RA-dependent mechanisms...
September 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28893957/anti-inflammatory-role-of-langerhans-cells-and-apoptotic-keratinocytes-in-ultraviolet-b-induced-cutaneous-inflammation
#17
Mayumi Hatakeyama, Atsushi Fukunaga, Ken Washio, Kumiko Taguchi, Yoshiko Oda, Kanako Ogura, Chikako Nishigori
UV radiation, particularly UVB, is the major risk factor for the induction of skin cancer, and it induces skin inflammation and immunosuppression. Although reports documented that Langerhans cells (LCs) play various roles in photobiology, little is known about whether they contribute to UVB-induced cutaneous inflammation. Recently, the anti-inflammatory effect of apoptotic cells was noted. This study focuses on the roles of LCs and apoptotic cells in UVB-induced cutaneous inflammation. We show that LCs are essential for resolution of UVB-induced cutaneous inflammation...
September 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28893956/cutting-edge-genetic-association-between-ifi16-single-nucleotide-polymorphisms-and-resistance-to-genital-herpes-correlates-with-ifi16-expression-levels-and-hsv-2-induced-ifn-%C3%AE-expression
#18
Kristina Eriksson, Alexandra Svensson, Alon S Hait, Kerstin Schlüter, Petra Tunbäck, Inger Nordström, Leonid Padyukov, Jan-Åke Liljeqvist, Trine H Mogensen, Søren R Paludan
IFN-γ-inducible protein 16 (IFI16) is an immunological DNA sensor proposed to act in the cyclic GMP-AMP synthase-stimulator of IFN genes pathway. Because mice do not have a clear ortholog of IFI16, this system is not suitable for genetic studies of IFI16. In this study, we have compared the dependency on IFI16, cyclic GMP-AMP synthase, and stimulator of IFN genes for type I IFN induction by a panel of pathogenic bacteria and DNA viruses. The IFN response induced by HSV-2 was particularly dependent on IFI16...
September 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28893955/nkg2d-signaling-between-human-nk-cells-enhances-tace-mediated-tnf-%C3%AE-release
#19
Neekun Sharma, Camille V Trinidad, Andrew P Trembath, Mary A Markiewicz
NK group 2 member D (NKG2D) is a strong NK cell-activating receptor, with engagement by ligands triggering granule release and cytokine production. The function of NKG2D signaling in NK cells has largely been studied in the context of engagement of the receptor by ligands expressed on the surface of target cells. We report that upon activation with IL-12, IL-15, and IL-18 human NK cells express NKG2D ligands of the UL16 binding protein family on the cell surface. NKG2D-ligand interaction between cytokine-stimulated NK cells increases the activity of the metalloprotease TNF-α-converting enzyme...
September 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28893954/the-orphan-nuclear-receptor-nr4a3-is-involved-in-the-function-of-dendritic-cells
#20
Masanori Nagaoka, Takuya Yashiro, Yuna Uchida, Tomoaki Ando, Mutsuko Hara, Hajime Arai, Hideoki Ogawa, Ko Okumura, Kazumi Kasakura, Chiharu Nishiyama
NR4A3/NOR1 belongs to the NR4A subfamily of the nuclear hormone receptor superfamily, which is activated in a ligand-independent manner. To examine the role of NR4A3 in gene expression of dendritic cells (DCs), we introduced NR4A3 small interfering RNA (siRNA) into bone marrow-derived DCs and determined the expression levels of mRNA and proteins of cytokines, cell surface molecules, NF-κB signaling-related proteins, and transcription factors. The expression level of NR4A3 was markedly upregulated by TLR-mediated stimulation in DCs...
September 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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