全身性自己免疫マウスモデルにおける自己抗体産生に対するT細胞の役割と腸内細菌の関与

学位の種別:課程博士University of Tokyo(東京大学

Ectopic or Over-Expression of Class 1 Phytoglobin Genes Confers Flooding Tolerance to the Root Nodules of Lotus japonicus by Scavenging Nitric Oxide

Flooding limits biomass production in agriculture. Leguminous plants, important agricultural crops, use atmospheric dinitrogen gas as nitrogen nutrition by symbiotic nitrogen fixation with rhizobia, but this root-nodule symbiosis is sometimes broken down by flooding of the root system. In this study, we analyzed the effect of flooding on the symbiotic system of transgenic Lotus japonicus lines which overexpressed class 1 phytoglobin (Glb1) of L. japonicus (LjGlb1-1) or ectopically expressed that of Alnus firma (AfGlb1). In the roots of wild-type plants, flooding increased nitric oxide (NO) level and expression of senescence-related genes and decreased nitrogenase activity; in the roots of transgenic lines, these effects were absent or less pronounced. The decrease of chlorophyll content in leaves and the increase of reactive oxygen species (ROS) in roots and leaves caused by flooding were also suppressed in these lines. These results suggest that increased levels of Glb1 help maintain nodule symbiosis under flooding by scavenging NO and controlling ROS

Measurement and Operational Improvement in an Office with Thermo Active Building System

Thermo Active Building System (TABS) is applied in office buildings in many European countries as a promising energy-efficient solution with a comfortable thermal environment. However, TABS is rarely applied in Japanese buildings because of the risk of dew condensation during the hot and humid summer season. In this study, the indoor environment and thermal sensation in an office building equipped with TABS was investigated; the building is located in an urban area in Tokyo, Japan. Soon after occupancy, field measurements and questionnaire surveys were conducted during the summer and winter seasons for two consecutive years. The operation of TABS was improved based on first-year measurement results. As a result, the ceiling surface setpoint temperature was relaxed, maintaining high satisfaction in summer. In winter, it was confirmed that the operation of TABS was not necessary, and, as a result, satisfaction improved

Stably Transformed Lotus japonicus Plants Overexpressing Phytoglobin LjGlb1-1 Show Decreased Nitric Oxide Levels in Roots and Nodules as Well as Delayed Nodule Senescence

33 Pags.- 1 Tabl.- 14 Figs. The definitive version is available at: https://academic.oup.com/pcpThe class 1 phytoglobin, LjGlb1-1, is expressed in various tissues of the model legume Lotus japonicus, where it may play multiple functions by interacting with nitric oxide (NO). One of such functions is the onset of a proper symbiosis with Mesorhizobium loti resulting in the formation of actively N2-fixing nodules. Stable overexpression lines (Ox1 and Ox2) of LjGlb1-1 were generated and phenotyped. Both Ox lines showed reduced NO levels in roots and enhanced nitrogenase activity in mature and senescent nodules relative to the wild-type (WT). Physiological and cytological observations indicated that overexpression of LjGlb1-1 delayed nodule senescence. The application to WT nodules of the NO donor S-nitroso-N-acetyl-DL-penicillamine (SNAP) or the phytohormones abscisic acid (ABA) and the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC) repressed nitrogenase activity, induced the expression of three senescence-associated genes and caused cytological changes evidencing nodule senescence. These effects were almost completely reverted by the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide. Our results reveal that overexpression of LjGlb1-1 improves the activity of mature nodules and delays nodule senescence in the L.japonicus–M.loti symbiosis. These beneficial effects are probably mediated by the participation of LjGlb1-1 in controlling the concentration of NO that may be produced downstream in the phytohormone signaling pathway in nodules.Open Partnership Joint Projects of the Japanese Society for the Promotion of Science (JSPS) Bilateral Joint Research Projects (Japan) and National Institute for Basic Biology (NIBB) Collaborative Research Program [16-305 and 17-309, Japan to T.U.]; the Ministry of Economy and Competitiveness [AGL2017-85775-R, Spain to M.B.]; and JSPS KAKENHI Research Fellows [JP18J11872, Japan to M.F.].Peer reviewe

Defects in mucosal immunity and nasopharyngeal dysbiosis in HSC transplanted SCID patients with IL2RG/JAK3 deficiency

International audienceBoth innate and adaptive lymphocytes have critical roles in mucosal defense that contain commensal microbial communities and protect against pathogen invasion. Here we characterize mucosal immunity in human severe combined immunodeficiency (SCID) patients receiving hematopoietic stem cell transplantation (HSCT) with or without myeloablation. We confirmed that pre-transplant conditioning impacted on innate (NK, ILC) and adaptive (B and T cells) lymphocyte reconstitution in these SCID patients and now demonstrate that this further extends to generation of Th2 and Tc2 cells. Using an integrated approach to assess nasopharyngeal immunity, we identify a local mucosal defect in type 2 cytokines, mucus production and a selective local IgA deficiency in HSCT-treated SCID patients with genetic defects in IL2RG/GC or JAK3. These patients have a reduction in IgA-coated nasopharyngeal bacteria and exhibit microbial dysbiosis with increased pathobiont carriage. Interestingly, IVIG replacement therapy can partially normalize nasopharyngeal Ig profiles and restore microbial communities in GC/JAK3 patients. Together, our results suggest a potential non-redundant role for type 2 immunity and/or of local IgA antibody production in the maintenance of nasopharyngeal microbial homeostasis and mucosal barrier function

A human immune system (HIS) mouse model that dissociates roles for mouse and human FcR + cells during antibody‐mediated immune responses

Human immune system (HIS) mice provide a model to study human immune responses in vivo. Currently available HIS mouse models may harbor mouse Fc Receptor (FcR)‐expressing cells that exert potent effector functions following administration of human Ig. Previous studies showed that the ablation of the murine FcR gamma chain (FcR‐γ) results in loss of antibody‐dependent cellular cytotoxicity and antibody‐dependent cellular phagocytosis in vivo. We created a new FcR‐γ‐deficient HIS mouse model to compare host (mouse) versus graft (human) effects underlying antibody‐mediated immune responses in vivo. FcR‐γ‐deficient HIS recipients lack expression and function of mouse activating FcRs and can be stably and robustly reconstituted with human immune cells. By screening blood B‐cell depletion by rituximab Ig variants, we found that human FcγRs‐mediated IgG1 effects, whereas mouse activating FcγRs were dominant in IgG4 effects. Complement played a role as an IgG1 variant (IgG1 K322A) lacking complement binding activity was largely ineffective. Finally, we provide evidence that FcγRIIIA on human NK cells could mediate complement‐independent B‐cell depletion by IgG1 K322A. We anticipate that our FcR‐γ‐deficient HIS model will help clarify mechanisms of action of exogenous administered human antibodies in vivo