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International Immunology

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https://www.readbyqxmd.com/read/29202179/extensively-reorganized-systemic-lymph-nodes-provide-a-feasible-environment-for-self-reactivity-in-lupus-prone-nzb-nzw-f1-mice
#1
Yoichi Kurosawa, Madoka Ozawa, Yasuhiro Kanda, Arata Takeuchi, Toshihiko Kawamura, Ichiei Narita, Tomoya Katakai
Lymphadenopathy is a frequently observed symptom in systemic lupus erythematosus, although the immunological role of lymph nodes (LNs) in systemic autoimmunity remains largely unknown. Here, we performed comprehensive and systematic analyses of LNs in lupus-prone NZB × NZW F1 (BWF1) mice, demonstrating extensive tissue reorganization of the systemic LNs with follicular expansion, hyper germinal center (GC) formation, atrophy of the paracortical T cell area, and expansion of the medulla in aged BWF1 mice bearing glomerulonephritis...
November 30, 2017: International Immunology
https://www.readbyqxmd.com/read/29186424/nalt-m-cells-are-important-for-immune-induction-for-the-common-mucosal-immune-system
#2
Yasuhiro Date, Masashi Ebisawa, Shinji Fukuda, Hideaki Shima, Yuuki Obata, Daisuke Takahashi, Tamotsu Kato, Misaho Hanazato, Gaku Nakato, Ifor R Williams, Koji Hase, Hiroshi Ohno
Nasopharynx-associated lymphoid tissue (NALT) is one of the major constituents of the mucosa-associated lymphoid tissue (MALT), and has the ability to induce antigen-specific immune responses. However, the molecular mechanisms responsible for antigen uptake from the nasal cavity into the NALT remain largely unknown. Immunohistochemical analysis showed that CCL9 and CCL20 were co-localized with GP2 in the epithelium covering NALT, suggesting the existence of M cells in NALT. In analogy with the reduced number of Peyer's patch M cells in CCR6-deficient mice, the number of NALT M cells was drastically decreased in CCR6-deficient mice compared to the wild-type mice...
November 27, 2017: International Immunology
https://www.readbyqxmd.com/read/29155995/lysosome-biogenesis-regulated-by-the-amino-acid-transporter-slc15a4-is-critical-for-functional-integrity-of-mast-cells
#3
Toshihiko Kobayashi, Hidemitsu Tsutsui, Shiho Shimabukuro-Demoto, Reiko Sugitani-Yoshida, Hitomi Karyu, Kaori Furuyama-Tanaka, Daisuke Ohshima, Norihiro Kato, Tadashi Okamura, Noriko Toyama Sorimachi
Mast cells possess specialized lysosomes, so-called secretory granules, which play a key role not only in allergic responses but also in various immune disorders. The molecular mechanisms that control secretory-granule formation are not fully understood. Solute carrier family member 15A4 (SLC15A4) is a lysosome-resident amino-acid/oligopeptide transporter that is preferentially expressed in hematopoietic-lineage cells. Here we demonstrated that SLC15A4 is required for mast-cell secretory granule homeostasis, and limits mast-cell functions and inflammatory responses by controlling the mTORC1-TFEB signaling axis...
November 15, 2017: International Immunology
https://www.readbyqxmd.com/read/29136157/depletion-of-recombination-specific-co-factors-by-the-c-terminal-mutant-of-the-activation-induced-cytidine-deaminase-causes-the-dominant-negative-effect-on-class-switch-recombination
#4
Azza Al Ismail, Afzal Husain, Maki Kobayashi, Tasuku Honjo, Nasim A Begum
Activation-induced cytidine deaminase (AID) is essential for class-switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin (Ig) genes. Studies on in vitro mutagenized AID as well as its mutations in human patients with Hyper-IgM (HIGM)-syndrome type II revealed that C-terminal AID mutations were defective in CSR whereas their DNA cleavage and SHM activities remained intact. The C-terminal mutants of AID were speculated to exert the dominant negative effect on wild type WT AID whereas its mechanism remains unknown...
November 10, 2017: International Immunology
https://www.readbyqxmd.com/read/29121254/impact-of-donor-and-recipient-human-cytomegalovirus-status-on-kidney-transplantation
#5
Maciej Zielinski, Agnieszka Tarasewicz, Hanna Zielinska, Magdalena Jankowska, Grazyna Moszkowska, Alicja Debska-Slizien, Boleslaw Rutkowski, Piotr Trzonkowski
Human cytomegalovirus (HCMV) is considered to be a major pathogen that affects the outcome of solid organ transplantation. Both recipient and donor may be HCMV positive, therefore HCMV reinfection is possible after transplantation. However, little is known how cytomegalovirus transmitted from an infected donor to an infected recipient modulates the recipient's already suppressed immunity, and what the clinical consequences are. To investigate these issues, 52 kidney recipients were followed up for two years after transplantation...
November 7, 2017: International Immunology
https://www.readbyqxmd.com/read/29126272/generation-of-alloantigen-specific-induced-treg-stabilized-by-vitamin-c-treatment-and-its-application-for-prevention-of-acute-graft-versus-host-disease-model
#6
Hidenori Kasahara, Taisuke Kondo, Hiroko Nakatsukasa, Shunsuke Chikuma, Minako Ito, Makoto Ando, Yutaka Kurebayashi, Takashi Sekiya, Taketo Yamada, Shinichiro Okamoto, Akihiko Yoshimura
Antigen-specific regulatory T cells (Tregs) possess the potential to reduce excess immune responses in autoimmune diseases, allergy, rejection after organ transplantation, and graft-versus-host disease (GVHD) in hematopoietic stem-cell transplantation. Although in vitro-expanded antigen-specific induced Tregs (iTregs) have been considered to be a promising therapeutic agent against such excessive immune reactions, the instability of iTregs after transfer is a fundamental problem in their clinical application...
November 4, 2017: International Immunology
https://www.readbyqxmd.com/read/29106601/flexible-fate-commitment-of-e2-2high-common-dc-progenitors-implies-tuning-in-tissue-microenvironments
#7
Nobuyuki Onai, Jumpei Asano, Rumiko Kurosaki-Nakamura, Shoko Kuroda, Toshiaki Ohteki
The basic helix-loop-helix transcription factor E2-2 is essential for the development of plasmacytoid dendritic cells (pDCs) but not conventional DCs (cDCs). Here, we generated E2-2 reporter mice and demonstrated that an E2-2high fraction among common DC progenitors (CDPs), which are a major source of pDCs and cDCs in the steady state, strictly gave rise to pDCs in the presence of Flt3 ligand ex vivo or in the secondary lymphoid organs when transferred in vivo. However, in the small intestine, some of these E2-2high progenitors differentiated into cDCs that produced retinoic acid...
November 2, 2017: International Immunology
https://www.readbyqxmd.com/read/29106539/spontaneous-chondroma-formation-in-cd2-cre-driven-erk-deficient-mice
#8
Moe Shiokawa, Xiuyuan Lu, Yasunobu Miyake, Eri Ishikawa, Gilles Pagès, Jacques Pouysségur, Masato Ogata, Sho Yamasaki
Lineage-specific Cre Tg mice are widely used to delineate the functions of genes in a tissue-specific manner. Several T cell-specific promoter cassettes have been developed, however, the activities of those promoters in non-T cells have not been investigated extensively. Here, we report that CD2-Cre-mediated deletion of Erk proteins by generating CD2-Cre × Erk1-/-Erk2flox/flox (Erk∆CD2-Cre) mice results in abnormal cartilage hyperplasia. Histological analysis revealed that this abnormality is caused by aberrant hyperplasia of chondrocytes...
November 2, 2017: International Immunology
https://www.readbyqxmd.com/read/29069431/targeted-antibody-therapy-and-relevant-novel-biomarkers-for-precision-medicine-for-rheumatoid-arthritis
#9
Yuko Kaneko, Tsutomu Takeuchi
Over the past two decades, the management of rheumatoid arthritis has progressed remarkably, encompassing the development of new diagnostic tools and efficacious biological agents, such as monoclonal antibodies against inflammatory cytokines and surface markers on immune cells. In addition to the significant efficacy of these biological agents, biomarkers for rheumatoid arthritis are under consideration for their potential to classify heterogeneous patients into several groups based on clinical and immunological phenotypes for the prediction of clinical course and prognosis and the facilitation of appropriate and precise treatment with the appropriate therapeutic monoclonal antibodies...
October 24, 2017: International Immunology
https://www.readbyqxmd.com/read/29099971/involvement-of-zizimin2-3-in-the-age-related-defect-of-peritoneal-b-1a-cells-as-a-source-of-anti-bacterial-igm
#10
Akihiko Sakamoto, Takenori Matsuda, Koichiro Kawaguchi, Akinori Takaoka, Mitsuo Maruyama
Zizimin2 (Ziz2), also known as dedicator of cytokinesis 11 (DOCK11), is a guanine nucleotide exchange factor that is predominantly expressed in lymphoid tissues. Recent findings demonstrated that Ziz2 is involved in the development of B cells, including germinal centre B cells and marginal zone B cells. However, limited information is currently available on the roles of Ziz2 in B-1 cells, a B-cell subset that resides in body cavities and contributes to protection against foreign pathogens in a T-cell-independent manner...
November 1, 2017: International Immunology
https://www.readbyqxmd.com/read/29099970/expression-of-kir2ds1-does-not-significantly-contribute-to-nk-cell-cytotoxicity-in-hla-c1-c2-heterozygous-haplotype-b-donors
#11
Karla Baltner, Ayline Kübler, Marina Pal, Monika Balvociute, Markus Mezger, Rupert Handgretinger, Maya C André
NK cells are functionally controlled by the killer immunoglobulin-like receptor (KIR) family that comprises inhibitory (iKIR) and activating (aKIR) members. Genetic association studies suggest that donors expressing aKIRs next to iKIRs will be superior donors in the setting of hematopoietic stem cell transplantation of patients with leukemia. However, contrary evidence states that aKIR expression may be irrelevant or even detrimental. Using a complex methodology incorporating KIR-Q-PCR, double fluorescence and viSNE analysis, we characterized subset distribution patterns and functionality in haplotype A donors which lack aKIRs and haplotype B donors that express a variety of B-specific genes...
November 1, 2017: International Immunology
https://www.readbyqxmd.com/read/29099969/anti-tumor-immunity-via-the-superoxide-eosinophil-axis-induced-by-a-lipophilic-component-of-mycobacterium-lipomannan
#12
Toshihiro Ito, Kiyoshi Hirahara, Atsushi Onodera, Ryo Koyama-Nasu, Ikuya Yano, Toshinori Nakayama
Mycobacterium bovis Bacille Calmette-Guérin (BCG) has been shown to possess potent anti-tumor activity particularly in various animal models, while the cellular and molecular mechanisms underlying its activity are not well understood. We found that lipomannan (BCG-LM), a lipophilic component of the mycobacterial cell envelope, specifically inhibits tumor growth and induces the infiltration of eosinophils at local tumor invasion sites. In contrast, neither lipoarabinomannan (BCG-LAM) nor the cell wall of Mycobacterium bovis BCG (BCG-CW) exerted anti-tumor immunity...
November 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28541437/hyperferritinemia-and-inflammation
#13
Kate F Kernan, Joseph A Carcillo
Understanding of ferritin biology has traditionally centered on its role in iron storage and homeostasis, with low ferritin levels indicative of deficiency and high levels indicative of primary or secondary hemochromatosis. However, further work has shown that iron, redox biology and inflammation are inexorably linked. During infection, increased ferritin levels represent an important host defense mechanism that deprives bacterial growth of iron and protects immune cell function. It may also be protective, limiting the production of free radicals and mediating immunomodulation...
November 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28387826/a-clinical-update-on-inflammasomopathies
#14
Hafize Emine Sönmez, Seza Özen
Inflammasomes are important elements of the innate immune defense. The most common autoinflammatory syndromes, as well a number of rare ones, are due to hereditary defects in the inflammasomes, hence are called inflammasomopathies. The recent clinical advances in these diseases will be reviewed, with special emphasis on reflecting the international collaborative work in the field. Recent recommendations for familial Mediterranean fever, cryopyrin-associated periodic syndromes and hyper-IgD syndrome/mevalonate kinase deficiency will be presented and diagnostics tests, treatment alternatives and follow-up recommendations will be summarized...
November 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28992076/autoimmunity-associated-with-chemically-induced-thymic-dysplasia
#15
Daisuke Nagakubo, Jeremy B Swann, Stefanie Birmelin, Thomas Boehm
Autoimmune and inflammatory conditions are a frequent complication in patients with reduced numbers of T cells. Here, we describe a mouse model of thymic stromal dysplasia resulting in peripheral T cell lymphopenia. In Foxn1:CFP-NTR transgenic mice, the bacterial nitroreductase enzyme is expressed in thymic epithelial cells and converts the prodrug CB1954 into a cytotoxic agent. This strategy enables titratable and durable destruction of thymopoietic tissue in early embryogenesis. Our results indicate that the resulting low levels of thymic capacity for T cell production create a predisposition for the development of a complex autoimmune syndrome, chiefly characterized by inflammatory bowel disease and lymphocytic organ infiltrations...
September 12, 2017: International Immunology
https://www.readbyqxmd.com/read/28992059/the-human-naip-nlrc4-inflammasome-senses-the-pseudomonas-aeruginosa-t3ss-inner-rod-protein
#16
Grandjean Teddy, Boucher Anne, Thepaut Marion, Monlezun Laura, Guery Benoit, Faudry Eric, Kipnis Eric, Dessein Rodrigue
While NLRC4-dependent sensing of intracellular Gram-negative pathogens such as Salmonella Typhimurium is a beneficial host response, NLRC4-dependent sensing of the Pseudomonas aeruginosa type 3 secretion system (T3SS) has been shown to be involved in pathogenicity. In mice, different pathogen-associated microbial patterns are sensed by the combination of the NLRC4-inflammasome with different members of neuronal apoptosis inhibitory protein (NAIPs). NAIP2 is involved in sensing PscI, an inner-rod protein of the P...
August 28, 2017: International Immunology
https://www.readbyqxmd.com/read/29048538/improvement-of-foxp3-stability-through-cns2-demethylation-by-tet-enzyme-induction-and-activation
#17
Kazue Someya, Hiroko Nakatsukasa, Minako Ito, Taisuke Kondo, Kenn-Ichi Tateda, Takashi Akanuma, Ikuko Koya, Tsukasa Sanosaka, Jun Kohyama, Yu-Ichi Tsukada, Takeji Takamura-Enya, Akihiko Yoshimura
Since induced regulatory T cells (iTregs) can be produced in a large quantity in vitro, these cells are expected to be clinically useful to induce immunological tolerance in various immunological diseases. Foxp3 (Forkhead box P3) expression in iTregs is, however, unstable due to the lack of demethylation of the CpG island in the conserved non-coding sequence 2 (CNS2) of the Foxp3 locus. To facilitate the demethylation of CNS2, we over-expressed the catalytic domain (CD) of the ten-eleven translocation (TET) protein, which catalyzes the steps of the iterative demethylation of 5-methylcytosine...
August 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28992181/requirement-of-glycosylation-machinery-in-toll-like-receptor-responses-revealed-by-crispr-cas9-screening
#18
Ryota Sato, Takuma Shibata, Yu Tanaka, Chiharu Kato, Kiyoshi Yamaguchi, Yoichi Furukawa, Eigo Shimizu, Rui Yamaguchi, Seiya Imoto, Satoru Miyano, Kensuke Miyake
The Toll family of receptors sense microbial products and activate a defense response. The molecular machinery required for the Toll-like receptor (TLR) response is not yet fully understood. In the present study, we used a CRISPR/CAS9 screening system to study TLR responses. We employed a cell line expressing TLR with an NF-κB-driven GFP reporter. The cell line was transduced with a guide RNA library and stimulated with TLR ligands. The cells impaired in GFP induction were sorted, and gRNAs were sequenced...
July 28, 2017: International Immunology
https://www.readbyqxmd.com/read/28992252/uromodulin-slpa-binding-dictates-lactobacillus-acidophilus-uptake-by-intestinal-epithelial-m-cells
#19
Sae Yanagihara, Takashi Kanaya, Shinji Fukuda, Gaku Nakato, Misaho Hanazato, Xue-Ru Wu, Naoyuki Yamamoto, Hiroshi Ohno
Bacterial access to the gut immune system is a crucial process to promote host immune responses. The probiotic L-92 strain of Lactobacillus acidophilus exerts anti-allergic immunomodulatory effects upon oral administration in mice. Here we show that M cells are responsible for L-92 internalization for evoking L-92-mediated immune responses. L-92 specifically bound to uromodulin, a glycosylphosphatidylinositol-anchored protein expressed exclusively on M cells among intestinal epithelial cells. Internalization of L-92 into M cells was significantly reduced in uromodulin-deficient (Umod-/-) mice compared to Umod+/+ mice...
July 22, 2017: International Immunology
https://www.readbyqxmd.com/read/28910970/antibody-therapy-for-the-management-of-severe-asthma-with-eosinophilic-inflammation
#20
Ken Ohta, Hiroyuki Nagase, Maho Suzukawa, Shin Ohta
One of the characteristic features of asthma is chronic airway inflammation typically with eosinophil infiltration. Most asthmatics can be treated successfully with conventional treatment appropriate for their severity, but in some severe cases, asthma cannot be well controlled even with thorough treatment and this condition is known as 'refractory asthma'. To overcome severe refractory asthma, a new therapeutic strategy with biologics has been developed based on the knowledge of molecular mechanisms of airway inflammation in asthma, induced by the condition of high Th2-type responses and activation of eosinophils as well as allergic reactions...
July 1, 2017: International Immunology
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