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

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https://www.readbyqxmd.com/read/30446570/rapid-and-efficient-production-of-human-functional-mast-cells-through-a-three-dimensional-culture-of-adipose-tissue-derived-stromal-vascular-cells
#1
Jenny Paupert, Eric Espinosa, Nicolas Cenac, Virginie Robert, Patrick Laharrague, Solène M Evrard, Louis Casteilla, Anne Lorsignol, Béatrice Cousin
Mast cells (MC) are innate immune cells involved in many physiological and pathological processes. However, studies of MC function and biology are hampered by the difficulties to obtain human primary MC. To solve this problem, we established a new method to produce easily and rapidly high numbers of MC for in vitro studies using human adipose tissue, which is an abundant and easy access tissue. Stromal vascular fraction of adipose tissue, obtained from human abdominal dermolipectomy, was cultured as spheroids in serum free medium supplemented in stem cell factor...
November 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30446569/il-33-released-in-the-liver-inhibits-tumor-growth-via-promotion-of-cd4-and-cd8-t-cell-responses-in-hepatocellular-carcinoma
#2
Ziqi Jin, Lei Lei, Dandan Lin, Yonghao Liu, Yuan Song, Huanle Gong, Ying Zhu, Yu Mei, Bo Hu, Yan Wu, Guangbo Zhang, Haiyan Liu
IL-33 released by epithelial cells and immune cells functions as an alarmin and can induce both type 1 and type 2 immune responses. However, the role of IL-33 release in tumor development is still not clear. In this study, we examined the function of released IL-33 in murine hepatocellular carcinoma (HCC) models by hydrodynamically injecting either IL-33-expressing tumor cells or IL-33-expressing plasmids into the liver of tumor-bearing mice. Tumor growth was greatly inhibited by IL-33 release. This antitumor effect of IL-33 was dependent on suppression of tumorigenicity 2 (ST2) because it was diminished in ST2-/- mice...
November 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30446568/nonredundant-roles-of-il-21-and-il-4-in-the-phased-initiation-of-germinal-center-b-cells-and-subsequent-self-renewal-transitions
#3
David G Gonzalez, Christine M Cote, Jaymin R Patel, Colin B Smith, Yuqi Zhang, Kevin M Nickerson, Tingting Zhang, Steven M Kerfoot, Ann M Haberman
We examined the unique contributions of the cytokines IL-21 and IL-4 on germinal center (GC) B cell initiation and subsequent maturation in a murine model system. Similar to other reports, we found T follicular helper cell expression of IL-21 begins prior to T follicular helper cell migration into the B cell follicle and precedes that of IL-4. Consistent with this timing, IL-21 signaling has a greater influence on the perifollicular pre-GC B cell transition to the intrafollicular stage. Notably, Bcl6hi B cells can form in the combined absence of IL-21R- and STAT6-derived signals; however, these nascent GC B cells cease to proliferate and are more prone to apoptosis...
November 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30446567/surveillance-of-myelodysplastic-syndrome-via-migration-analyses-of-blood-neutrophils-a-potential-prognostic-tool
#4
Marc Schuster, Mischa Moeller, Lea Bornemann, Clara Bessen, Charlyn Sobczak, Saskia Schmitz, Laura Witjes, Katja Kruithoff, Christina Kohn, Olga Just, Andrea Kündgen, Noreen Pundt, Benedikt Pelzer, Christophe Ampe, Marleen Van Troys, Arnd Nusch, Rainer Haas, Ulrich Germing, Lennart Martens, Karl-Heinz Jöckel, Matthias Gunzer
Autonomous migration is a central characteristic of immune cells, and changes in this function have been correlated to the progression and severity of diseases. Hence, the identification of pathologically altered leukocyte migration patterns might be a promising approach for disease surveillance and prognostic scoring. However, because of the lack of standardized and robust assays, migration patterns have not been clinically exploited so far. In this study, we introduce an easy-to-use and cross-laboratory, standardized two-dimensional migration assay for neutrophil granulocytes from peripheral blood...
November 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30446566/colitis-promotes-a-pathological-condition-of-the-liver-in-the-absence-of-foxp3-regulatory-t-cells
#5
Franziska Mathies, Niklas Steffens, Doerte Kleinschmidt, Friederike Stuhlmann, Francis J Huber, Urmi Roy, Thomas Meyer, Marc Luetgehetmann, Mareike von Petersdorff, Oliver Seiz, Johannes Herkel, Christoph Schramm, Richard A Flavell, Nicola Gagliani, Christian Krebs, Ulf Panzer, Zeinab Abdullah, Till Strowig, Tanja Bedke, Samuel Huber
Inflammatory bowel disease is associated with extraintestinal diseases such as primary sclerosing cholangitis in the liver. Interestingly, it is known that an imbalance between Foxp3+ regulatory T cells (Treg) and Th17 cells is involved in inflammatory bowel disease and also in primary sclerosing cholangitis. To explain these associations, one hypothesis is that intestinal inflammation and barrier defects promote liver disease because of the influx of bacteria and inflammatory cells to the liver. However, whether and how this is linked to the Treg and Th17 cell imbalance is unclear...
November 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30446565/sialic-acid-dependent-inhibition-of-t-cells-by-exosomal-ganglioside-gd3-in-ovarian-tumor-microenvironments
#6
Gautam N Shenoy, Jenni Loyall, Charles S Berenson, Raymond J Kelleher, Vandana Iyer, Sathy V Balu-Iyer, Kunle Odunsi, Richard B Bankert
The tumor microenvironment is rendered immunosuppressive by a variety of cellular and acellular factors that represent potential cancer therapeutic targets. Although exosomes isolated from ovarian tumor ascites fluids have been previously reported to induce a rapid and reversible T cell arrest, the factors present on or within exosomes that contribute to immunosuppression have not been fully defined. In this study, we establish that GD3, a ganglioside expressed on the surface of exosomes isolated from human ovarian tumor ascites fluids, is causally linked to the functional arrest of T cells activated through their TCR...
November 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30446564/induction-of-a-long-noncoding-rna-transcript-nr_045064-promotes-defense-gene-transcription-and-facilitates-intestinal-epithelial-cell-responses-against-cryptosporidium-infection
#7
Min Li, Ai-Yu Gong, Xin-Tian Zhang, Yang Wang, Nicholas W Mathy, Gislaine A Martins, Juliane K Strauss-Soukup, Xian-Ming Chen
Cryptosporidium is an important opportunistic intestinal pathogen for immunocompromised individuals and a common cause of diarrhea in young children in developing countries. Gastrointestinal epithelial cells play a central role in activating and orchestrating host immune responses against Cryptosporidium infection, but underlying molecular mechanisms are not fully understood. We report in this paper that C. parvum infection causes significant alterations in long noncoding RNA (lncRNA) expression profiles in murine intestinal epithelial cells...
November 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30429288/predicting-humoral-alloimmunity-from-differences-in-donor-and-recipient-hla-surface-electrostatic-potential
#8
Dermot H Mallon, Christiane Kling, Matthew Robb, Eva Ellinghaus, J Andrew Bradley, Craig J Taylor, Dieter Kabelitz, Vasilis Kosmoliaptsis
In transplantation, development of humoral alloimmunity against donor HLA is a major cause of organ transplant failure, but our ability to assess the immunological risk associated with a potential donor-recipient HLA combination is limited. We hypothesized that the capacity of donor HLA to induce a specific alloantibody response depends on their structural and physicochemical dissimilarity compared with recipient HLA. To test this hypothesis, we first developed a novel computational scoring system that enables quantitative assessment of surface electrostatic potential differences between donor and recipient HLA molecules at the tertiary structure level [three-dimensional electrostatic mismatch score (EMS-3D)]...
November 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30429287/complement-inhibitor-crig-fh-ameliorates-renal-ischemia-reperfusion-injury-via-activation-of-pi3k-akt-signaling
#9
Chao Hu, Long Li, Peipei Ding, Ling Li, Xiaowen Ge, Long Zheng, Xuanchuan Wang, Jina Wang, Weitao Zhang, Na Wang, Hongyu Gu, Fan Zhong, Ming Xu, Ruiming Rong, Tongyu Zhu, Weiguo Hu
Complement activation is involved in the pathogenesis of ischemia reperfusion injury (IRI), which is an inevitable process during kidney transplantation. Therefore, complement-targeted therapeutics hold great potential in protecting the allografts from IRI. We observed universal deposition of C3d and membrane attack complex in human renal allografts with delayed graft function or biopsy-proved rejection, which confirmed the involvement of complement in IRI. Using FB -, C3 -, C4 -, C5 -, C5aR1 -, C5aR2 -, and C6 -deficient mice, we found that all components, except C5aR2 deficiency, significantly alleviated renal IRI to varying degrees...
November 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30429286/the-length-distribution-and-multiple-specificity-of-naturally-presented-hla-i-ligands
#10
David Gfeller, Philippe Guillaume, Justine Michaux, Hui-Song Pak, Roy T Daniel, Julien Racle, George Coukos, Michal Bassani-Sternberg
HLA-I molecules bind short peptides and present them for recognition by CD8+ T cells. The length of HLA-I ligands typically ranges from 8 to 12 aa, but variability is observed across different HLA-I alleles. In this study we collected recent in-depth HLA peptidomics data, including 12 newly generated HLA peptidomes (31,896 unique peptides) from human meningioma samples, to analyze the peptide length distribution and multiple specificity across 84 different HLA-I alleles. We observed a clear clustering of HLA-I alleles with distinct peptide length distributions, which enabled us to study the structural basis of peptide length distributions and predict peptide length distributions from HLA-I sequences...
November 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30429285/deregulated-auf1-assists-bmp-ezh2-mediated-delayed-wound-healing-during-candida-albicans-infection
#11
Kasturi Mahadik, Preeti Yadav, Bharat Bhatt, Riyaz Ahmad Shah, Kithiganahalli Narayanaswamy Balaji
Tissue repair is a complex process that necessitates an interplay of cellular processes, now known to be dictated by epigenetics. Intriguingly, macrophages are testimony to a large repertoire of evolving functions in this process. We identified a role for BMP signaling in regulating macrophage responses to Candida albicans infection during wound repair in a murine model. In this study, the RNA binding protein, AU-rich element-binding factor 1, was posttranslationally destabilized to bring about ubiquitin ligase, NEDD4-directed activation of BMP signaling...
November 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30429284/indole-3-pyruvic-acid-an-aryl-hydrocarbon-receptor-activator-suppresses-experimental-colitis-in-mice
#12
Reiji Aoki, Ayako Aoki-Yoshida, Chise Suzuki, Yoshiharu Takayama
Aryl hydrocarbon receptor (AHR) agonists are promising immunomodulators that potentially maintain immune tolerance. In this study, we examined the ability of indole-3-pyruvic acid (IPA), a major precursor of microbiota-derived AHR agonists and a proagonist of AHR, to activate AHR. The anti-inflammatory effects of IPA were also evaluated in a mouse model of colitis in comparison with other aromatic pyruvic acids (phenylpyruvic acid and 4-hydroxyphenylpyruvic acid). Among them, IPA showed the strongest ability to activate AHR in vitro and in vivo, and only IPA improved chronic inflammation in an experimental colitis model...
November 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30420438/talin1-methylation-is-required-for-neutrophil-infiltration-and-lipopolysaccharide-induced-lethality
#13
Thomas Jun Feng Lim, I-Hsin Su
Talin1, a well-established integrin coactivator, is critical for the transmigration of neutrophils across the vascular endothelium into various organs and the peritoneal cavity during inflammation. Several posttranslational modifications of talin1 have been proposed to play a role in this process. In this study, we show that trimethylation of talin1 at Lys2454 by cytosolic Ezh2 is substantially increased in murine peritoneal neutrophils upon induction of peritonitis. By reconstituting talin1-deficient mouse myeloid cells with wild-type, methyl-mimicking, or unmethylatable talin1 variants, we demonstrate that methylation of talin1 at Lys2454 is important for integrin-dependent neutrophil infiltration into the peritoneal cavity...
November 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30420437/cd8%C3%AE-dendritic-cells-dictate-leukemia-specific-cd8-t-cell-fates
#14
Douglas E Kline, Brendan W MacNabb, Xiufen Chen, Wen-Ching Chan, Dominick Fosco, Justin Kline
APCs are essential for the orchestration of antitumor T cell responses. Batf3-lineage CD8α+ and CD103+ dendritic cells (DCs), in particular, are required for the spontaneous initiation of CD8+ T cell priming against solid tumors. In contrast, little is known about the APCs that regulate CD8+ T cell responses against hematological malignancies. Using an unbiased approach, we aimed to characterize the APCs responsible for regulating CD8+ T cell responses in a syngeneic murine leukemia model. We show with single-cell resolution that CD8α+ DCs alone acquire and cross-present leukemia Ags in vivo, culminating in the induction of leukemia-specific CD8+ T cell tolerance...
November 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30420436/cutting-edge-b-cells-expressing-cyclic-citrullinated-peptide-specific-antigen-receptor-are-tolerized-in-normal-conditions
#15
Hisakata Yamada, Tatsuhiko Ozawa, Hiroyuki Kishi, Seiji Okada, Yasuharu Nakashima, Atsushi Muraguchi, Yasunobu Yoshikai
Generation of neoantigens by citrullination is implicated in the production of anti-citrullinated protein Abs in rheumatoid arthritis, but citrullination is also a physiological process. To verify whether citrullin-specific B cells are immunologically ignorant or tolerant in normal conditions, transgenic (Tg) mice expressing IgM with the V region of an anti-cyclic citrullinated peptide (CCP) mAb cloned from a rheumatoid arthritis patient were generated. CCP-specific B cells developed in the anti-CCP IgM Tg mice with an alteration of bone marrow B cell fractions, and the number of mature B cells decreased compared with wild-type or the control anti-influenza nucleoprotein-specific IgM Tg mice...
November 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30420435/brief-exposure-of-skin-to-near-infrared-laser-modulates-mast-cell-function-and-augments-the-immune-response
#16
Yoshifumi Kimizuka, Wataru Katagiri, Joseph J Locascio, Ayako Shigeta, Yuri Sasaki, Mai Shibata, Kaitlyn Morse, Ruxandra F Sîrbulescu, Mizuki Miyatake, Patrick Reeves, Makoto Suematsu, Jeffrey Gelfand, Timothy Brauns, Mark C Poznansky, Kosuke Tsukada, Satoshi Kashiwagi
The treatment of skin with a low-power continuous-wave (CW) near-infrared (NIR) laser prior to vaccination is an emerging strategy to augment the immune response to intradermal vaccine, potentially substituting for chemical adjuvant, which has been linked to adverse effects of vaccines. This approach proved to be low cost, simple, small, and readily translatable compared with the previously explored pulsed-wave medical lasers. However, little is known on the mode of laser-tissue interaction eliciting the adjuvant effect...
November 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30413672/cutting-edge-transcriptional-profiling-reveals-multifunctional-and-cytotoxic-antiviral-responses-of-zika-virus-specific-cd8-t-cells
#17
Alba Grifoni, Priscilla Costa-Ramos, John Pham, Yuan Tian, Sandy L Rosales, Grégory Seumois, John Sidney, Aruna D de Silva, Lakshmanane Premkumar, Matthew H Collins, Mars Stone, Phillip J Norris, Claudia M E Romero, Anna Durbin, Michael J Ricciardi, Julie E Ledgerwood, Aravinda M de Silva, Michael Busch, Bjoern Peters, Pandurangan Vijayanand, Eva Harris, Andrew K Falconar, Esper Kallas, Daniela Weiskopf, Alessandro Sette
Zika virus (ZIKV) constitutes an increasing public health problem. Previous studies have shown that CD8+ T cells play an important role in ZIKV-specific protective immunity. We have previously defined antigenic targets of the ZIKV-specific CD8+ T cell response in humans. In this study, we characterized the quality and phenotypes of these responses by a combined use of flow cytometry and transcriptomic methods, using PBMCs from donors deriving from different geographical locations collected in the convalescent phase of infection...
November 9, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30413671/multiplexed-fluorospot-for-the-analysis-of-dengue-virus-and-zika-virus-specific-and-cross-reactive-memory-b-cells
#18
Awadalkareem Adam, Marcia Woda, Sonia Kounlavouth, Alan L Rothman, Richard G Jarman, Josephine H Cox, Julie E Ledgerwood, Gregory D Gromowski, Jeffrey R Currier, Heather Friberg, Anuja Mathew
Dengue virus (DENV) and Zika virus (ZIKV) are mosquito-borne pathogens that have a significant impact on human health. Immune sera, mAbs, and memory B cells (MBCs) isolated from patients infected with one DENV type can be cross-reactive with the other three DENV serotypes and even more distantly related flaviviruses such as ZIKV. Conventional ELISPOTs effectively measure Ab-secreting B cells but because they are limited to the assessment of a single Ag at a time, it is challenging to distinguish serotype-specific and cross-reactive MBCs in the same well...
November 9, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30413670/the-transcription-factors-pu-1-and-irf4-determine-dendritic-cell-specific-expression-of-raldh2
#19
Takuya Yashiro, Masaki Yamaguchi, Yumi Watanuki, Kazumi Kasakura, Chiharu Nishiyama
RALDH2 expressed in dendritic cells (DCs) plays a critical role in the development of regulatory T cells in mesenteric lymph nodes. Despite the importance of RALDH2 in intestinal immunity, little is known about the mechanism of DC-specific expression of RALDH2. In the current study, we focused on the hematopoietic cell-specific transcription factors PU.1 and IRF4 as the determinants of Aldh1a2 gene expression. The mRNA level of Aldh1a2 , and subsequently the enzyme activity, were decreased by knockdown of PU...
November 9, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30404815/sublytic-c5b-9-induces-il-23-and-il-36a-production-by-glomerular-mesangial-cells-via-pcaf-mediated-klf4-acetylation-in-rat-thy-1-nephritis
#20
Jing Zhang, Mengxiao Xie, Lu Xia, Tianyi Yu, Fengxia He, Chenhui Zhao, Wen Qiu, Dan Zhao, Yu Liu, Yajuan Gong, Chunyan Yao, Longfei Liu, Yingwei Wang
Sublytic C5b-9 formation on glomerular mesangial cells in rat Thy-1 nephritis (Thy-1N), a model of human mesangioproliferative glomerulonephritis, is accompanied by the production of proinflammatory cytokines, but the relationship between sublytic C5b-9 and cytokine synthesis and the underlying mechanism remains unclear. To explore the problems mentioned above, in this study, we first examined the levels of proinflammatory ILs (e.g., IL-23 and IL-36a) as well as transcription factor (KLF4) and coactivator (PCAF) in the renal tissues of Thy-1N rats and in the glomerular mesangial cell line (HBZY-1) stimulated by sublytic C5b-9...
November 7, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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