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International Immunology

Kensuke Miyake, Takuma Shibata, Umeharu Ohto, Toshiyuki Shimizu, Shin-Ichiroh Saitoh, Ryutaro Fukui, Yusuke Murakami
Nucleic acid (NA)-sensing Toll-like receptors (TLRs) respond to DNA/RNA derived from pathogens and dead cells. Structural studies have revealed a variety of molecular mechanisms by which TLRs sense NAs. Double-stranded RNA and single-stranded DNA directly bind to TLR3 and TLR9, respectively, whereas TLR7 and 8 bind to nucleosides and oligoribonucleotides derived from RNAs. Activation of ligand-bound TLRs is influenced by the functional status of TLRs. Proteolytic cleavage of NA-sensing TLRs enables ligand-dependent TLR dimerization...
February 14, 2018: International Immunology
Ei Wakamatsu, Hiroki Omori, Yuki Tabata, Yuki Akieda, Shiho Watanabe, Shuhei Ogawa, Ryo Abe
It is well-established that CD28 co-stimulation is required for the development and the proliferation of thymus-derived regulatory T cells (tTregs). Meanwhile, the role of CD28 co-stimulation in the homeostasis of peripherally-derived Tregs (pTregs) remains unclear. To clarify this issue, we analyzed Tregs in small and large intestines (SI and LI), the principle sites of pTreg development. Interestingly, and different from in the thymus, Tregs were abundant in the intestines of CD28-/- mice, and most of them were phenotypically pTregs...
February 7, 2018: International Immunology
Caroline Fraga Cabral Gomes Nunes, Jeane S Nogueira, Fábio B Canto, Pedro Henrique Oliveira Vianna, Bianca Torres Ciambarella, Patrícia Machado Rodrigues E Silva, Karla Rodrigues Miranda, Leandro Araújo Lobo, Regina Maria Cavalcanti Pillotto Domingues, Mileane Busch, Georgia Correa Atella, André Macedo Vale, Maria Bellio, Alberto Nóbrega, Rita Fucs
The incidence of allergic diseases, which increased to epidemic proportions in developed countries over the last few decades, has been correlated with altered gut microbiota colonization. Although probiotics may play a critical role on the restoration of gut homeostasis, its efficiency on the control of allergy is controversial. Here we aimed to investigate the effects of probiotic treatment initiated at neonatal or adult ages on the suppression of experimental ovalbumin-induced asthma. Neonatal or adult mice were orally treated with probiotic bacteria and subjected to ovalbumin-induced allergy...
February 6, 2018: International Immunology
Grant S Schulert, Scott W Canna
Hyperferritinemia and pronounced hemophagocytosis help distinguish a subset of patients with a particularly inflammatory and deadly systemic inflammatory response syndrome. Two clinically similar disorders typify these hyperferritinemic syndromes: hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS). HLH is canonically associated with a complete disturbance of perforin/granzyme-mediated cytotoxicity, whereas MAS occurs in the context of the related rheumatic diseases systemic juvenile idiopathic arthritis (SJIA) and adult-onset Still's disease (AOSD), with associated IL-1 family cytokine activation...
February 6, 2018: International Immunology
Miwa Sasai, Ariel Pradipta, Masahiro Yamamoto
Toxoplasma gondii can infect homoeothermic animals including humans and cause lethal toxoplasmosis in immunocompromised individuals. When hosts are infected with T. gondii, the cells induce immune responses against T. gondii. The pathogen infection is recognized by immune sensors that directly detect T. gondii structural components, leading to production of proinflammatory cytokines and chemokines. Antigen-presenting cells such as macrophages and dendritic cells strongly activate T cells and induce development of Th1 cells and antigen-specific killer CD8 T cells...
February 2, 2018: International Immunology
Koichi Hirose, Takashi Ito, Hiroshi Nakajima
Asthma is a chronic inflammatory disease of the airways that is characterized by eosinophilic inflammation, mucus hypersecretion and airway remodeling that leads to airway obstruction. Although these pathognomonic features of asthma are primarily mediated by allergen-specific T helper type 2 cells (Th2 cells) and their cytokines, recent studies have revealed critical roles of lung epithelial cells in the pathogenesis of asthma. Lung epithelial cells not only form physical barriers by covering the surfaces of the airways but also sense inhaled allergens and initiate communication between the environment and the immune system...
January 31, 2018: International Immunology
Marcus Lettau, Fred Armbrust, Katharina Dohmen, Lisann Drews, Tobias Poch, Michelle Dietz, Dieter Kabelitz, Ottmar Janssen
It is widely accepted that cytotoxic T and NK cells store effector proteins including granzymes, perforin and FasL in intracellular granules, often referred to as secretory lysosomes. Upon target cell encounter, these organelles are transported to the cytotoxic immunological synapse, where they fuse with the plasma membrane to release the soluble effector molecules and to expose transmembrane proteins including FasL on the cell surface. We previously described two distinct species of secretory vesicles in T and NK cells that differ in size, morphology and protein loading, most strikingly regarding FasL and granzyme B...
January 24, 2018: International Immunology
Hisashi Ueta, Yusuke Kitazawa, Yasushi Sawanobori, Takamasa Ueno, Satoshi Ueha, Kouji Matsushima, Kenjiro Matsuno
Donor-specific blood transfusion is known to induce alloresponses and lead to immunosuppression. We examined their underlying mechanisms by employing fully allogeneic rat combinations. Transfused recipients efficiently produced alloantibodies of the IgM and IgG subclasses directed against donor class I MHC. The recipients exhibited active expansion of CD4+ T-cells and CD4+FOXP3+ Treg cells, followed by CD45R+ B-cells and IgM+ or IgG subclass+ antibody-forming cells mainly in the spleen. From 1.5 days, the resident MHCII+CD103+ dendritic cells in the splenic T-cell area, periarterial lymphocyte sheath, formed clusters with recipient BrdU+ or 5-ethynyl-2'-deoxyuridine+ cells, from which the proliferative response of CD4+ T-cells originated peaking at 3-4 days...
January 18, 2018: International Immunology
Anne T Mai, Wei Lue Tong, Yaping N Tu, George Blanck
Renal cell carcinoma exome-derived, V(D)J recombination reads had an elevated presence and variability, for both TcR-α and β, when compared to marginal tissue, reflecting an opportunity to assess tumor immunogenicity by comparison with marginal tissue T-cells. PD-1, PD-L2, CTLA4, and FOXP3, all of which are implicated in the evasion of an anti-tumor immune response, had a significantly higher expression for samples representing co-detection of productive TcR-⍺ and -β recombination reads. Samples representing tumors with productive TcR-α recombination reads but no detectable, productive TcR-β recombination reads, reflected a 20% survival advantage, and RNASeq data indicated an intermediate level of immune checkpoint gene expression for those samples...
January 18, 2018: International Immunology
Tomomi Uchida, Hisashi Ueta, Xue-Dong Xu, Jotaro Hirakawa, Kazunori Tahara, Shu Zhou, Yasushi Sawanobori, Szandor Simmons, Yusuke Kitazawa, Hiroto Kawashima, Kenjiro Matsuno
Naive lymphocytes systemically recirculate for immunosurveillance inspecting foreign antigens and pathogens in the body. Trafficking behavior such as the migration pathway and transit time within the gastrointestinal tract, however, remains to be elucidated. Rat thoracic duct lymphocytes (TDLs) were transferred to a congeneic host that had undergone mesenteric lymphadenectomy. The migration pathway was investigated using newly developed four-color immunohistochemistry and immunofluorescence. Donor TDLs showed rapid transition in gut tissues from which they emerged in mesenteric lymph around 4 h after intravenous injection...
January 16, 2018: International Immunology
Takefumi Yamashita
Because antibodies have become an important therapeutic tool, rational antibody design is a challenging issue involving various science and technology fields. From the computational aspect, many types of design-assist methods have been developed, but their accuracy is not fully satisfactory. Because of recent advancements in computational power, molecular dynamics (MD) simulation has become a helpful tool to trace the motion of proteins and to characterize their properties. Thus, MD simulation has been applied to various systems involving antigen-antibody complexes and has been shown to provide accurate insight into antigen-antibody interactions and dynamics at an atomic resolution...
January 15, 2018: International Immunology
Koubun Yasuda, Kenji Nakanishi
Helminth infection remains common in developing countries, where residents who suffer from the consequences of such infections can develop serious physical and mental disorders and often persist in the face of serious economic problems. Intestinal nematode infection induces the development of Th2-type immune responses including the B cell IgE response; additionally, this infection induces an increase in the numbers and activation of various types of effector cells, such as mast cells, eosinophils and basophils, as well as the induction of goblet cell hyperplasia, antimicrobial peptide production and smooth muscle contraction, all of which contribute to expel nematodes...
January 13, 2018: International Immunology
Judith-Irina Buchheim, Spencer Hoskyns, Dominique Moser, Bing Han, Elisabeth Deindl, Marion Hörl, Katharina Biere, Matthias Feuerecker, Gustav Schelling, Alexander Chouker
A prolonged stress burden is known to hamper the efficiency of both the innate and adaptive immune systems and to attenuate the stress responses by the catecholaminergic and endocannabinoid (EC) systems. Key mechanisms of innate immunity are the eradication of pathogens through phagocytosis and the respiratory burst. We tested the concentration-dependent, spontaneous and stimulated (via TNFα and fMLP) release of reactive oxygen species (ROS) by human PMNs in vitro in response to norepinephrine (NE) and AM1241, a pharmacological ligand for the endocannabinoid receptor CB2...
January 10, 2018: International Immunology
Michelle Sue Jann Lee, Cevayir Coban
Individuals from malaria-endemic regions often acquire partial immunity after multiple repeated infections throughout their lives. This partial immunity prevents them from developing severe complications and they often remain asymptomatic with a persistent, low parasite density in the blood, and therefore the necessity for treatment is neglected. These patients with chronic, asymptomatic malaria serve as a reservoir for Plasmodium parasite transmission, becoming a major obstacle for eradication efforts. The constant exposure to malaria infection may have benefits in the short term by conferring protection from acute, severe malaria; however, it may cause substantially more harm in the long term...
December 28, 2017: International Immunology
Yoshiko Takeuchi, Atsushi Tanemura, Yasuko Tada, Ichiro Katayama, Atsushi Kumanogoh, Hiroyoshi Nishikawa
Cancer immunotherapy that blocks immune checkpoint molecules, such as PD-1/PD-L1, unleashes dysfunctional antitumor T-cell responses and has durable clinical benefits in various types of cancers. Yet its clinical efficacy is limited to a small proportion of patients, highlighting the need for identifying biomarkers that can predict the clinical response by exploring antitumor responses crucial for tumor regression. Here we explored T-cell responses associated with clinical benefits using peripheral blood mononuclear cells (PBMCs) from patients with malignant melanoma treated with anti-PD-1 monoclonal antibody (mAb)...
December 23, 2017: International Immunology
Matteo Rossi, Nicolas Fasel
Infection by protozoan parasites of the genus Leishmania results in the development of leishmaniases, an increasingly prevalent group of diseases affecting over 12 million people worldwide. Leishmaniasis can have very different outcomes ranging from cutaneous lesions, mucosal lesions to visceralization depending on the species of the infecting parasite and on the immune response developed by the host. As an obligate intracellular parasite, residing within macrophages, Leishmania evolved in strict contact with the host immune system, developing different mechanisms to evade or modulate the immune response...
December 23, 2017: International Immunology
Toru Atsumi, Hironao Suzuki, Jing-Jing Jiang, Yuko Okuyama, Ikuma Nakagawa, Mitsutoshi Ota, Yuki Tanaka, Takuto Ohki, Kokichi Katsunuma, Koichi Nakajima, Yoshinori Hasegawa, Osamu Ohara, Hideki Ogura, Yasunobu Arima, Daisuke Kamimura, Masaaki Murakami
Rbm10 is a RNA binding protein that regulates alternative splicing, but its role in inflammation is not well defined. Here we show that Rbm10 controls appropriate splicing of Dnmt3b, a DNA methyltransferase, to regulate the activity of NFκB-responsive promoters and consequently inflammation development. Rbm10 deficiency suppressed NFκB-mediated responses in vivo and in vitro. Mechanistic analysis showed that Rbm10 deficiency decreased promoter recruitment of NFκB, with increased DNA methylation of the promoter regions in NFκB-responsive genes...
December 22, 2017: International Immunology
Akira Shibuya, Shin-Ichiro Honda, Kazuko Shibuya
Fc receptors play important roles for a wide array of immune responses. In contrast to the well-defined Fcγ and Fcε receptors, the molecular and functional characteristics of Fc receptors for IgA and IgM have remained incompletely understood for years. Recent progress has unveiled the characteristics of Fc receptors for IgA and IgM, including Fcα/μ receptor (Fcα/μR) (CD351), polymeric immunoglobulin receptor (poly-IgR), Fcα receptor (FcαRI) (CD89) and Fcμ receptor (FcμR). In this review, we summarize the molecular and functional characteristics of Fcα/μR in comparison with poly-IgR, FcμR and FcαRI, and focus particularly on the pro-inflammatory function of Fcα/μR expressed on marginal zone B cells in sepsis...
December 21, 2017: International Immunology
Tatsukuni Ohno, Chenyang Zhang, Yuta Kondo, Siwen Kang, Emi Furusawa, Kimitake Tsuchiya, Yasunari Miyazaki, Miyuki Azuma
V-domain Ig suppressor of T cell activation (VISTA) is a novel immune checkpoint receptor and ligand that regulates T cell activation. We investigated the functional involvement of VISTA in Th2 cell-mediated immune responses using an ovalbumin (OVA)-induced allergic asthma model. Treatment with an anti-VISTA monoclonal antibody (mAb) during allergen sensitization increased the production of antibodies, including total IgE, OVA-specific IgG1 and IgG2a, and allergen-specific interleukin (IL)-5 and IL-13; it also increased the expression of IL-13 by splenic CD4 + T cells...
December 15, 2017: International Immunology
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
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