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International Immunology

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https://www.readbyqxmd.com/read/28992076/autoimmunity-associated-with-chemically-induced-thymic-dysplasia
#1
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
#2
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/28992181/requirement-of-glycosylation-machinery-in-toll-like-receptor-responses-revealed-by-crispr-cas9-screening
#3
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/29048538/improvement-of-foxp3-stability-through-cns2-demethylation-by-tet-enzyme-induction-and-activation
#4
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/28992252/uromodulin-slpa-binding-dictates-lactobacillus-acidophilus-uptake-by-intestinal-epithelial-m-cells
#5
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
#6
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
https://www.readbyqxmd.com/read/28910969/polymorphisms-of-immunoglobulin-receptors-and-the-effects-on-clinical-outcome-in-cancer-immunotherapy-and-other-immune-diseases-a-general-review
#7
Tomonori Kaifu, Akira Nakamura
Receptors for the Fc domain of immunoglobulins [Fc receptors (FcRs)] are essential for the maintenance of antibody-mediated immune responses. FcRs consist of activating- and inhibitory-type receptors that regulate adequate thresholds for various immune cells. In particular, polymorphisms and/or gene copy-number variations of FcRs for IgG (FcγRs) are closely associated with the development of inflammatory disorders, including autoimmune diseases. Recent evidence has implicated polymorphisms of FcRs in the efficacy of monoclonal antibody (mAb)-mediated therapy...
July 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28910968/efficiency-of-antibody-therapy-in-demyelinating-diseases
#8
Tetsuya Akaishi, Ichiro Nakashima
Monoclonal antibody therapy is a new treatment strategy for many types of diseases including cancers and autoimmune diseases, realizing a high efficacy and tolerability. In multiple sclerosis (MS) and neuromyelitis optica (NMO) spectrum disorders, several monoclonal antibodies have been suggested to decrease the incidence of clinical relapse and the disease activity. In MS, anti-α4 integrin (natalizumab), anti-CD52 (alemtuzumab), anti-CD25 (daclizumab) and anti-CD20 (ocrelizumab) have been shown to effectively reduce the relapses in randomized controlled trials and have been approved by the Food and Drug Administration...
July 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28655198/glycosylation-of-igg-fc-a-molecular-perspective
#9
Masato Kiyoshi, Kouhei Tsumoto, Akiko Ishii-Watabe, Jose M M Caaveiro
Antibodies of the IgG class carry a pair of oligosaccharides (N-glycans) in the Fc region. The importance of the N-glycan is clearly demonstrated by its profound effect in the physicochemical and biological properties of antibodies. The term 'glycoengineering' has been coined to describe contemporary strategies to improve the performance of therapeutic monoclonal antibodies on the basis of modifications in the structure and composition of the N-glycan. These methodologies have resulted in the approval and commercialization of a new generation of antibodies with improved therapeutic efficacy...
July 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28472280/diversification-of-igg-effector-functions
#10
Stylianos Bournazos, Jeffrey V Ravetch
IgG is the major immunoglobulin class produced during an immune response against foreign antigens and efficiently provides protection through its bifunctional nature. While the Fab domains confer highly specific recognition of the antigen, the Fc domain mediates a wide range of effector functions that modulate several aspects of innate and adaptive immunity. Engagement of the various types of Fcγ receptors (FcγRs) by an IgG Fc domain can activate distinct immunomodulatory pathways with pleiotropic functional consequences for several leukocyte types...
July 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28666326/ivig-mediated-effector-functions-in-autoimmune-and-inflammatory-diseases
#11
Caroline Galeotti, Srini V Kaveri, Jagadeesh Bayry
Intravenous immunoglobulin (IVIG) is a pooled preparation of normal immunoglobulin IgG obtained from several thousand healthy donors. It is widely used in the immunotherapy of a large number of autoimmune and inflammatory diseases. The mechanisms of action of IVIG are complex and, as discussed in this review, experimental and clinical data provide an indicator that the therapeutic benefit of IVIG therapy is due to several mutually nonexclusive mechanisms affecting soluble mediators as well as cellular components of the immune system...
June 28, 2017: International Immunology
https://www.readbyqxmd.com/read/28814067/neuro-immune-interactions-in-allergic-diseases-novel-targets-for-therapeutics
#12
Tiphaine Voisin, Amélie Bouvier, Isaac M Chiu
Recent studies have highlighted an emerging role for neuro-immune interactions in mediating allergic diseases. Allergies are caused by an overactive immune response to a foreign antigen. The peripheral sensory and autonomic nervous system densely innervates mucosal barrier tissues including the skin, respiratory tract and gastrointestinal (GI) tract that are exposed to allergens. It is increasingly clear that neurons actively communicate with and regulate the function of mast cells, dendritic cells, eosinophils, Th2 cells and type 2 innate lymphoid cells in allergic inflammation...
June 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28814066/mice-expressing-human-erap1-variants-associated-with-ankylosing-spondylitis-have-altered-t-cell-repertoires-and-nk-cell-functions-as-well-as-increased-in-utero-and-perinatal-mortality
#13
David P W Rastall, Fadel S Alyaquob, Patrick O'Connell, Yuliya Pepelyayeva, Douglas Peters, Sarah Godbehere-Roosa, Cristiane Pereira-Hicks, Yasser A Aldhamen, Andrea Amalfitano
Specific variants of endoplasmic reticulum-associated aminopeptidase 1 (ERAP1) identified by genome-wide association study modify the risk for developing ankylosing spondylitis. We previously confirmed that disease-associated ERAP1 variants have altered enzymatic abilities that can impact upon the production of pro-inflammatory cytokines from cells expressing the same ERAP1 variants. To determine if these ERAP1 variants also impacted immune responses in vivo, we generated two strains of transgenic mice expressing human ERAP1 genes containing non-synonymous single-nucleotide polymorphisms associated with an increased (ERAP1-High) or decreased (ERAP1-Low) risk for developing autoimmune disease...
June 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28637300/commercial-rodent-diets-differentially-regulate-autoimmune-glomerulonephritis-epigenetics-and-microbiota-in-mrl-lpr-mice
#14
Michael R Edwards, Rujuan Dai, Bettina Heid, Thomas E Cecere, Deena Khan, Qinghui Mu, Catharine Cowan, Xin M Luo, S Ansar Ahmed
The course and severity of lupus in spontaneous murine lupus models varies among laboratories, which may be due to variations in diet, housing and/or local environmental conditions. In this study, we investigated the influence of common rodent diets while keeping other factors constant. Female lupus-prone MRL/lpr (MRL/MpJ-Faslpr/J) mice were subjected to the same housing conditions and given one of the three diets: Teklad 7013 containing isoflavone-rich soy and alfalfa, Harlan 2018 isoflavone-rich soy-based diet or Research Diets Inc...
June 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28575522/identification-of-biomarker-sets-for-predicting-the-efficacy-of-sublingual-immunotherapy-against-pollen-induced-allergic-rhinitis
#15
Minoru Gotoh, Osamu Kaminuma, Akihiro Nakaya, Kazufumi Katayama, Yuji Motoi, Nobumasa Watanabe, Mayumi Saeki, Tomoe Nishimura, Noriko Kitamura, Kazuko Yamaoka, Kimihiro Okubo, Takachika Hiroi
Sublingual immunotherapy (SLIT) is effective against allergic rhinitis, although a substantial proportion of individuals is refractory. Herein, we describe a predictive modality to reliably identify SLIT non-responders (NRs). We conducted a 2-year clinical study in 193 adult patients with Japanese cedar pollinosis, with biweekly administration of 2000 Japanese allergy units of cedar pollen extract as the maintenance dose. After identifying high-responder (HR) patients with improved severity scores and NR patients with unchanged or exacerbated symptoms, differences in 33 HR and 34 NR patients were evaluated in terms of peripheral blood cellular profiles by flow cytometry and serum factors by ELISA and cytokine bead array, both pre- and post-SLIT...
June 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28541437/hyperferritinemia-and-inflammation
#16
Kate 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 protect immune cell function. It may also be protective, limiting the production of free radicals and mediating immunomodulation...
May 25, 2017: International Immunology
https://www.readbyqxmd.com/read/28541554/activation-of-group-2-innate-lymphoid-cells-exacerbates-and-confers-corticosteroid-resistance-to-mouse-nasal-type-2-inflammation
#17
Taiyo Morikawa, Ayumi Fukuoka, Kazufumi Matsushita, Koubun Yasuda, Naruhito Iwasaki, Shoko Akasaki, Shigeharu Fujieda, Tomohiro Yoshimoto
Both Th2 cells and group 2 innate lymphoid cells (ILC2s) contribute to allergic diseases. However, their exact role and relationship in nasal allergic disorders are unclear. In this study, we investigated the cooperation of Th2 cells and ILC2s in a mouse model of nasal allergic disorder. To differentially activate Th2 cells and/or ILC2s in nasal mucosa, mice were intra-nasally administered ovalbumin (OVA) antigen, papain, an ILC2-activator, or both for 2 weeks. Epithelial thickness and number of eosinophils in the nasal mucosa were evaluated at 24 h after the final challenge...
May 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28541550/integrity-of-immunoglobulin-variable-regions-is-supported-by-ganp-during-aid-induced-somatic-hypermutation-in-germinal-center-b-cells
#18
Mohammed Mansour Abbas Eid, Mayuko Shimoda, Shailendra Kumar Singh, Sarah Ameen Almofty, Phuong Pham, Myron F Goodman, Kazuhiko Maeda, Nobuo Sakaguchi
Immunoglobulin affinity maturation depends on somatic hypermutation (SHM) in immunoglobulin variable (IgV) regions initiated by activation-induced cytidine deaminase (AID). AID induces transition mutations by C→U deamination on both strands, causing C:G→T:A. Error-prone repairs of U by base excision and mismatch repairs (MMRs) create transversion mutations at C/G and mutations at A/T sites. In Neuberger's model, it remained to be clarified how transition/transversion repair is regulated. We investigate the role of AID-interacting GANP (germinal center-associated nuclear protein) in the IgV SHM profile...
May 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28541425/corrigendum
#19
(no author information available yet)
No abstract text is available yet for this article.
May 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28531279/mechanisms-governing-inflammasome-activation-assembly-and-pyroptosis-induction
#20
Sannula Kesavardhana, Thirumala-Devi Kanneganti
Inflammasomes are multimeric protein complexes that regulate inflammatory responses and pyroptotic cell death to exert host defense against microbes. Intracellular pattern-recognition receptors such as nucleotide-binding domain and leucine-rich repeat receptors (NLRs) and absent in melanoma 2 like receptors (ALRs) assemble the inflammasome complexes in response to pathogens and danger or altered-self signals in the cell. Inflammasome sensors, in association with an adaptor protein-apoptosis-associated speck-like protein containing a caspase-activation and -recruitment domain (ASC)-activate inflammatory caspase-1 to enable the release of inflammatory cytokines and induce cell death, conferring host defense against pathogens...
May 1, 2017: International Immunology
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