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International Immunology

Cordelia Manickam, Haiying Li, Spandan V Shah, Kyle Kroll, R Keith Reeves
Natural killer cells are primary immune effector cells with both innate and potentially adaptive functions against viral infections, but commonly become exhausted or dysfunctional during chronic diseases such as HIV. Chimpanzees are the closest genetic relatives of humans and have been previously used in immunology, behavior, and disease models. Due to their similarities to humans, a better understanding of chimpanzee immunology, particularly innate immune cells, can lend insight into the evolution of human immunology, as well as response to disease...
November 12, 2018: International Immunology
Bart G Jones, Robert E Sealy, Rhiannon R Penkert, Sherri L Surman, Robert W Maul, Geoff Neale, Beisi Xu, Patricia J Gearhart, Julia L Hurwitz
Nuclear hormone receptors including the estrogen receptor (ERα) and the retinoic acid receptor regulate a plethora of biological functions including reproduction, circulation, and immunity. To understand how estrogen and other nuclear hormones influence antibody production, we characterized total serum antibody isotypes in female and male mice of C57BL/6J, BALB/cJ, and C3H/HeJ mouse strains. Antibody levels were higher in females compared to males in all strains and there was a female preference for IgG2b production...
November 8, 2018: International Immunology
Jayaum S Booth, Eric Goldberg, Seema A Patil, Robin S Barnes, Bruce D Greenwald, Marcelo B Sztein
Our current understanding of CD4+ T cell mediated immunity (CMI) elicited by the oral live attenuated typhoid vaccine Ty21a is primarily derived from studies using peripheral blood. Very limited data is available in humans regarding mucosal immunity (especially CD4+ T) at the site of infection (e.g., terminal ileum; TI). Here using multiparametric flow cytometry, we examined the effect of Ty21a immunization on TI lamina propria mononuclear cells (LPMC) and peripheral blood CD4+ T memory (TM) subsets in volunteers undergoing routine colonoscopy...
October 20, 2018: International Immunology
Amit Singhal, Catherine Youting Cheng
Nicotinamide adenine dinucleotide (NAD+) is both a crucial coenzyme and a cosubstrate for various metabolic reactions in all living cells. Maintenance of NAD+ levels is essential for cell energy homeostasis, survival, proliferation and function. Mounting evidence points to NAD+ as one of the major modulators of immuno-metabolic circuits, thus regulating immune responses and functions. Recent studies delineate impaired host NAD+ metabolism during chronic infections and inflammation, suggesting NAD+ replenishment as an avenue to ameliorate deleterious inflammatory responses...
October 17, 2018: International Immunology
Koji Hosomi, Atsushi Hinenoya, Hidehiko Suzuki, Takahiro Nagatake, Tomomi Nishino, Yoko Tojima, So-Ichiro Hirata, Ayu Matsunaga, Masuo Kondoh, Shinji Yamasaki, Jun Kunisawa
Food poisonings caused by Clostridium perfringens and Shiga toxin (Stx)-producing Escherichia coli (STEC) occur frequently worldwide; however, no vaccine is currently available. Therefore, we aimed to develop a bivalent vaccine against C. perfringens and STEC infections. Although it has been considered that C-terminal region of C. perfringens enterotoxin (C-CPE) could be a good vaccine antigen to block the binding to its receptor, it was insufficient for induction of protective immune response due to the low antigenicity...
October 16, 2018: International Immunology
Akihiko Murata, Mari Hikosaka, Miya Yoshino, Lan Zhou, Shin-Ichi Hayashi
Kit/CD117 plays a crucial role in the cell-cell and cell-matrix adhesion of mammalian mast cells (MCs); however, it is unclear whether other adhesion molecule(s) perform important roles in the adhesion of MCs. In the present study, we show a novel Kit-independent adhesion mechanism of mouse cultured MCs mediated by Notch family members. On stromal cells transduced with each Notch ligand gene, Kit and its signaling become dispensable for the entire adhesion process of MCs from tethering to spreading. The Notch-mediated spreading of adherent MCs involves the activation of phosphatidylinositol 3-kinases and mitogen-activated protein kinases signaling, similar to Kit-mediated spreading...
October 8, 2018: International Immunology
Tetsuya Nakamura
The intestinal epithelium not only acts as the physical structure that separates the intestinal lumen from the body but also actively participates in intestinal barrier functions. In the past decade, significant progress has been made in the development of culture technologies to maintain intestinal epithelial cells (IECs) as various forms of intestinal organoids. As these organoids allow for restoration of the physiological composition of IECs, they represent suitable models to study the mechanisms of development and differentiation or the molecular basis of functions in specific types of IECs, such as goblet cells, Paneth cells, tuft cells and M cells...
October 3, 2018: International Immunology
Satoshi Fujiyama, Chigusa Nakahashi-Oda, Fumie Abe, Yaqiu Wang, Kazuki Sato, Akira Shibuya
Tissue resident macrophages in the spleen, including red pulp and white pulp macrophages, marginal zone macrophages (MZMs), and marginal zone metallophilic macrophages (MMMs), are highly heterogeneous as a consequence of adaptation to tissue-specific environments. Each macrophage subpopulation in the spleen is usually identified based on the localization, morphology and membrane antigen expression by immunohistochemistry. However, their phenotypical and functional characteristics remain incompletely understood due to the difficulty of identification and isolation by flow cytometry...
September 25, 2018: International Immunology
Takeshi Tsuda, Yohei Maeda, Masayuki Nishide, Shohei Koyama, Yoshitomo Hayama, Satoshi Nojima, Hyota Takamatsu, Daisuke Okuzaki, Yuhei Kinehara, Yasuhiro Kato, Takeshi Nakatani, Sho Obata, Hitoshi Akazawa, Takashi Shikina, Kazuya Takeda, Masaki Hayama, Hidenori Inohara, Atsushi Kumanogoh
Eosinophilic chronic rhinosinusitis (ECRS) is a subtype of chronic rhinosinusitis (CRS) that is characterized by intractable nasal polyp formation. Eosinophil-derived neurotoxin (EDN) is an eosinophil granule protein that is closely related to allergic inflammation, but the pathological implications of EDN in ECRS remain unknown. In this study, we evaluated the function of EDN in ECRS pathogenesis and assessed its potential as a disease activity marker. Serum EDN levels were significantly higher in patients with ECRS than in those with other nasal and paranasal diseases, and were positively correlated with clinical disease activity...
September 15, 2018: International Immunology
Toshihisa Nagao, Yoshinori Yamanishi, Kensuke Miyake, Mio Teranishi, Saori Takahashi, Soichiro Yoshikawa, Yohei Kawano, Hajime Karasuyama
Hapten is a small molecule that is not immunogenic on its own but can stimulate the production of antibodies at the sensitization phase when conjugated to carrier proteins. The hapten then reacts specifically with the antibodies generated against it to elicit an immune or allergic response at the challenge phase. Here we compared various carrier proteins conjugated with the same hapten in their ability to induce hapten-specific IgE-mediated allergic responses in vitro and in vivo, and characterized the nature of carrier proteins that determines the magnitude of response at the challenge phase of allergic reactions...
September 15, 2018: International Immunology
Koji Yasutomo
Immunoproteasomes degrade ubiquitin-coupled proteins and play a role in creating peptides for presentation by MHC class I proteins. Studies of gene-deficient mice in which each immunoproteasomal subunit was affected have demonstrated that dysfunction of immunoproteasomes leads to immunodeficiency, i.e., reduced expression of MHC class I and attenuation of CD8 T cell responses. Recent studies, however, have uncovered a new type of autoinflammatory syndrome characterized by fever, nodular erythema and progressive partial lipodystrophy that is caused by genetic mutations in immunoproteasome subunits...
August 31, 2018: International Immunology
Tatsuki Sugiyama, Yoshiki Omatsu, Takashi Nagasawa
The special microenvironments, termed niches, with which hematopoietic stem cells (HSCs) are in contact, have been thought to be required for the maintenance of HSCs and the generation of immune cells in bone marrow. Although the identity of the HSC niche has been a subject of long-standing debate, recent findings demonstrate that a population of mesenchymal stem cells, termed CXC chemokine ligand (CXCL)12-abundant reticular (CAR) cells or leptin receptor-expressing (LepR +) cells, are the major cellular components of niches for HSCs and lymphoid progenitors, which express specific transcription factors, including Foxc1 and Ebf3, and cytokines, including CXCL12 and stem cell factor (SCF), essential for their niche functions...
August 29, 2018: International Immunology
Michihito Katayama, Kaori Ota, Noriko Nagi-Miura, Naohito Ohno, Norikazu Yabuta, Hiroshi Nojima, Atsushi Kumanogoh, Toru Hirano
Previously, we reported that mRNA expression of ficolin-1 (FCN1), a component of the complement lectin pathway, is elevated in peripheral blood mononuclear cells of patients with vasculitis syndrome, and that FCN1-positive cells infiltrate into inflamed regions in patient specimens. In addition, we reported that serum FCN1 concentration is elevated in patients with Kawasaki disease (KD), a pediatric vasculitis, but dramatically decreases after intravenous immunoglobulin (IVIG) treatment. Furthermore, we showed that FCN1 binds to IgG1 in a pull-down assay...
August 28, 2018: International Immunology
Masaaki Kawano, Rie Takagi, Kikue Saika, Masanori Matsui, Sho Matsushita
Dopamine (DA) is synthesized by various immune cells. DA receptors (DARs), which comprise five isoforms, are expressed on the surface of these cells. Therefore, it is likely that DA plays a role in regulating innate and adaptive responses. However, the underlying molecular mechanism(s) is largely unknown. Here, we found that, during innate immune responses, DA suppressed secretion of IFN-γ, TNF-α and IL-1β, but promoted secretion of IL-10 and CXCL1 by lipopolysaccharide (LPS)-stimulated mouse splenocytes, suggesting that DA regulates cytokine secretion...
November 14, 2018: International Immunology
Mahiru Kawano, Shigekazu Nagata
An enormous number of cells in the body die by apoptosis during development and under homeostasis. Apoptotic cells are swiftly engulfed by macrophages and digested into units. This removal of apoptotic cells is called 'efferocytosis'. For efferocytosis, macrophages recognize phosphatidylserine (PtdSer) exposed on the cell surface as an 'eat me' signal. In healthy cells, PtdSer is exclusively localized to the inner leaflet of the plasma membrane by the action of flippases. When cells undergo apoptosis, caspase cleaves flippases to inactivate them, while it cleaves pro-scramblases to active scramblases, which quickly translocate PtdSer to the cell surface...
November 14, 2018: International Immunology
Chao-Yuan Tsai, Shuhei Sakakibara, Teruhito Yasui, Takeharu Minamitani, Daisuke Okuzaki, Hitoshi Kikutani
Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1), which mimics a constitutively active receptor, is required for viral transformation of primary B cells. LMP1 is expressed in EBV-infected germinal center (GC) B cells of immunocompetent individuals, suggesting that it may contribute to persistent EBV infection. In this study, we generated and analyzed mice that expressed LMP1 under the control of the CD19 or activation-induced cytidine deaminase (AID) promoter. Expression of LMP1 induced activation of B cells but severely inhibited their differentiation into antibody-secreting cells (ASCs) in vitro and GC B cells in vivo...
November 14, 2018: International Immunology
Andrea Franco, Zachary Kraus, Huifang Li, Naomi Seibert, Jessica Dement-Brown, Mate Tolnay
The B-cell response to antigen is critically regulated by co-receptors. CD21 (complement receptor 2) amplifies the response to antigen linked to its ligands, specific C3 fragments. In contrast, human Fc receptor-like 5 (FCRL5), a novel IgG receptor, was reported to inhibit B-cell receptor (BCR) signaling. Here, we show that CD21 and FCRL5 physically associate, suggesting that immune complexes containing both C3 fragment and IgG could simultaneously engage the pre-assembled receptors. We found that activating signaling molecules such as CD19, active PLCγ2 and BTK were rapidly recruited to FCRL5 upon engagement, suggesting a novel activating function for FCRL5...
November 14, 2018: International Immunology
Jastaranpreet Singh, Juan Carlos Zúñiga-Pflücker
T lymphocytes are critical mediators of the adaptive immune system and they can be harnessed as therapeutic agents against pathogens and in cancer immunotherapy. T cells can be isolated and expanded from patients and potentially generated in vitro using clinically relevant systems. An ultimate goal for T-cell immunotherapy is to establish a safe, universal effector cell type capable of transcending allogeneic and histocompatibility barriers. To this end, human pluripotent stem cells offer an advantage in generating a boundless supply of T cells that can be readily genetically engineered...
November 14, 2018: International Immunology
Yukiyoshi Mita, Motoko Y Kimura, Koji Hayashizaki, Ryo Koyama-Nasu, Toshihiro Ito, Shinichiro Motohashi, Yoshitaka Okamoto, Toshinori Nakayama
The introduction of immune checkpoint inhibitors in cancer treatment highlights the negative regulation of anti-tumor immunity, such as effector T-cell exhaustion in the tumor microenvironment. However, the mechanisms underlying the induction and prevention of T-cell exhaustion remain largely unknown. We found that CD69, a type II glycoprotein known to regulate inflammation through T-cell migration and retention in tissues, plays an important role in inducing the exhaustion of tumor-infiltrating T cells. Cd69-/- mice showed reduced tumor growth and metastasis in a 4T1-luc2 murine breast cancer model, in which increased numbers of tumor-infiltrating lymphocytes, relatively little T-cell exhaustion, and enhanced IFNγ production were observed...
November 14, 2018: International Immunology
Yasutaka Okabe
Macrophages are present in virtually almost all tissues, exhibiting highly heterogeneous phenotypes as a consequence of adaptation to local tissue environments. Tissue-resident macrophages perform specialized functions that are essential for the maintenance of tissue homeostasis, and abnormalities of their functions are linked to various pathologies. Recent advances have shown that tissue-specific transcriptional programs are responsible for functional specialization of macrophages in different tissues. Here, I discuss the molecular basis of tissue-resident macrophage specialization and how it is regulated by tissue environmental cues...
October 29, 2018: International Immunology
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