Pivotal Role of Dendritic Cell–derived CXCL10 in the Retention of T Helper Cell 1 Lymphocytes in Secondary Lymph Nodes

Various immune diseases are considered to be regulated by the balance of T helper (Th)1 and Th2 subsets. Although Th lymphocytes are believed to be generated in draining lymph nodes (LNs), in vivo Th cell behaviors during Th1/Th2 polarization are largely unexplored. Using a murine granulomatous liver disease model induced by Propionibacterium acnes, we show that retention of Th1 cells in the LNs is controlled by a chemokine, CXCL10/interferon (IFN) inducible protein 10 produced by mature dendritic cells (DCs). Hepatic LN DCs preferentially produced CXCL10 to attract 5′-bromo-2′-deoxyuridine (BrdU)+CD4+ T cells and form clusters with IFN-γ–producing CD4+ T cells by day 7 after antigen challenge. Blockade of CXCL10 dramatically altered the distribution of cluster-forming BrdU+CD4+ T cells. BrdU+CD4+ T cells in the hepatic LNs were selectively diminished while those in the circulation were significantly increased by treatment with anti-CXCL10 monoclonal antibody. This was accompanied by accelerated infiltration of memory T cells into the periphery of hepatic granuloma sites, most of them were in cell cycle and further produced higher amount of IFN-γ leading to exacerbation of liver injury. Thus, mature DC-derived CXCL10 is pivotal to retain Th1 lymphocytes within T cell areas of draining LNs and optimize the Th1-mediated immune responses

A promoter haplotype of the interleukin-18 gene is associated with juvenile idiopathic arthritis in the Japanese population

Recently, we reported that genetic polymorphisms within the human IL18 gene were associated with disease susceptibility to adult-onset Still's disease (AOSD), which is characterized by extraordinarily high serum levels of IL-18. Because high serum IL-18 induction has also been observed in the systemic type of juvenile idiopathic arthritis (JIA), we investigated whether similar genetic skewing is present in this disease. Three haplotypes, S01, S02, and S03, composed of 13 genetic polymorphisms covering two distinct promoter regions, were determined for 33 JIA patients, including 17 with systemic JIA, 10 with polyarthritis, and 6 with oligoarthritis. Haplotypes were also analyzed for 28 AOSD patients, 164 rheumatoid arthritis (RA) patients, 102 patients with collagen diseases, and 173 healthy control subjects. The frequency of individuals carrying a diplotype configuration (a combination of two haplotypes) of S01/S01 was significantly higher in the JIA patients, including all subgroups, than in the healthy controls (P = 0.0045, Fischer exact probability test; odds ratio (OR) = 3.55, 95% confidence interval (CI) = 1.55–8.14). In patients with systemic JIA, its frequency did not differ statistically from that of normal controls. Nevertheless, it is possible that haplotype S01 is associated with the phenotype of high IL-18 production in systemic JIA because the patients carrying S01/S01 showed significantly higher serum IL-18 levels compared with patients with other diplotype configurations (P = 0.017, Mann-Whitney U test). We confirmed that the frequency of the diplotype configuration of S01/S01 was significantly higher in AOSD patients than in healthy control subjects (P = 0.011, OR = 3.45, 95% CI = 1.42–8.36). Furthermore, the RA patients were also more predisposed to have S01/S01 (P = 0.018, OR = 2.00, 95% CI = 1.14–3.50) than the healthy control subjects, whereas the patients with collagen diseases did not. In summary, the diplotype configuration of S01/S01 was associated with susceptibility to JIA as well as AOSD and RA, and linked to significantly higher IL-18 production in systemic JIA. Possession of the diplotype configuration of S01/S01 would be one of the genetic risk factors for susceptibility to arthritis in the Japanese population

The conditional chalky grain mutant ’flo11-2ʹ of rice (Oryza sativa L.) is sensitive to high temperature and useful for studies on chalkiness

Chalky grains of rice are increased due to high temperature (HT) during a ripening period. However, the underlying mechanisms of the chalkiness are not well known, seemingly due to the obtuse response of wild type and lack of effective mutants. In this study, we isolated and characterized the flo11-2 mutant, which showed higher number of chalky grains than wild type under HT but quite small number of chalkiness under cool temperature as well as similar growth, development, and yield to that of the wild type. Using this high sensitivity of the flo11-2 mutant, we identified the most critical meteorological factor and developmental stage affecting chalkiness with 5 days HT treatments over 4 consecutive years. The results demonstrated that daily maximum temperature was more causative than daily mean or minimum temperatures which have been regarded as important factors before this. Besides, the developmental stage around 20 days after flowering (DAF) was most sensitive to HT rather than the early stage up to 15 DAF. In addition, we found that the flo11-2 mutant with a high chalky ratio was vulnerable to preharvest sprouting, which has never been reported before for chalky grains, but could cause significant yield and quality loss after extremely hot and dry summers followed by rainy cool autumns. The flo11-2 mutant is, therefore, a useful material for chalky grain research. Abbreviations: Tmax: Daily maximum temperature; Tmean: Daily mean temperature; Tmin: Daily minimum temperature; DAF: Days after flowering; DAH: Days after heading; Ext30: Excess temperature above 30 ºC; HDT: High day temperature; HNDT: High night and high day temperature; HNT: High night temperature; HT; High temperature; HTR: High temperature resistant; HTS: High temperature susceptible; BW: Basal white; MW: Milky white; WB: White back

Analysis of the Hepatic Functional Reserve, Portal Hypertension, and Prognosis of Patients With Human Immunodeficiency Virus/Hepatitis C Virus Coinfection Through Contaminated Blood Products in Japan

Background As the survival of human immunodeficiency virus (HIV)-infected individuals has improved due to the widespread use of antiretroviral therapy, the mortality rate due to hepatitis C virus (HCV)-related liver disease has increased in HIV/HCV-coinfected patients. Aim The aims of this study were to establish the appropriate therapeutic strategy for HIV/HCV-coinfected patients by evaluating the liver function, including the hepatic functional reserve and portal hypertension, and to investigate the prognosis of HIV/HCV-coinfected patients in Japan. Patients and Methods In addition to regular liver function tests, the hepatic functional reserve of 41 patients with HIV/HCV coinfection was evaluated using the indocyanine green retention rate and liver galactosyl serum albumin-scintigraphy. The data for 146 patients with HIV/HCV coinfection through blood products were extracted from 4 major HIV centers in Japan. In addition to liver function tests, the platelet counts (PLT) were evaluated as a marker of portal hypertension. Results In spite of the relatively preserved general liver function test results, approximately 40% of the HIV/HCV-coinfected patients had an impaired hepatic functional reserve. In addition, while the albumin and bilirubin levels were normal, the PLT was <150,000/μL in 17 patients. Compared with HCV mono-infected patients with a PLT <150,000/μL, the survival of HIV/HCV-coinfected patients was shorter (HCV, 5 years, 97%; 10 years, 86% and HIV/HCV, 5 years, 87%; 10 years, 73%; P <.05). Conclusion These results must be taken into account to establish an optimal therapeutic strategy, including the appropriate timing of liver transplantation in HIV/HCV-coinfected patients in Japan

Differentiation of core promoter architecture between plants and mammals revealed by LDSS analysis

Mammalian promoters are categorized into TATA and CpG-related groups, and they have complementary roles associated with differentiated transcriptional characteristics. While the TATA box is also found in plant promoters, it is not known if CpG-type promoters exist in plants. Plant promoters contain Y Patches (pyrimidine patches) in the core promoter region, and the ubiquity of these beyond higher plants is not understood as well. Sets of promoter sequences were utilized for the analysis of local distribution of short sequences (LDSS), and approximately one thousand octamer sequences have been identified as promoter constituents from Arabidopsis, rice, human and mouse, respectively. Based on their localization profiles, the identified octamer sequences were classified into several major groups, REG (Regulatory Element Group), TATA box, Inr (Initiator), Kozak, CpG and Y Patch. Comparison of the four species has revealed three categories: (i) shared groups found in both plants and mammals (TATA box), (ii) common groups found in both kingdoms but the utilized sequence is differentiated (REG, Inr and Kozak) and (iii) specific groups found in either plants or mammals (CpG and Y Patch). Our comparative LDSS analysis has identified conservation and differentiation of promoter architectures between higher plants and mammals

Argon-ion beam induced mutants of the ectomycorrhizal agaricomycete Tricholoma matsutake defective in β-1,4 endoglucanase activity promote the seedling growth of Pinus densiflora in vitro

Tricholoma matsutake is an ectomycorrhizal agaricomycete that produces the prized matsutake mushroom in conifer forests. Here, we isolated mutants generated by the argon-ion beam irradiation of T. matsutake NBRC 33136, designated as Ar 5002 and Ar 5012, which are defective in β-1,4 endoglucanase activity, that promoted the above- and below-ground growth of the symbiotic partner Pinus densiflora in vitro compared with the control. Pine seedlings associated with Ar 5002, compared with NBRC 33136, had significantly higher above-ground dry weights and significantly greater plant growth, while those associated with Ar 5012 had significantly higher above- and below-ground dry weights. There were no significant differences between the numbers of mycorrhizal root-tips synthesized by the wild-type and mutants, indicating that β-1,4 endoglucanase did not influence the mycorrhization of T. matsutake. In Ar 5002- and Ar 5012-inoculated seedlings, the Hartig nets resembled those of NBRC 33136-inoculated seedlings. The data suggest that T. matsutake lacking β-1,4 endoglucanase activity confer beneficial effects on P. densiflora growth. Further studies are necessary to determine whether the symbiotic relationship could be strengthened by such a mutated fungal trait.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Ion Beam Mutagenesis - an Innovative and Effective Method for Plant Breeding and Gene Discovery

We have developed a unique technology for mutation induction of plants using energetic ion beams at the RI Beam Factory (RIBF) of Rikagaku Kenkyūjo (RIKEN) (Institute of Physical and Chemical Research). Ion beams effectively induce mutations at relatively low doses without severely inhibiting growth. The irradiation treatment can be given to various plant materials and mutation can be induced in a short time, between seconds and a few minutes. The linear energy transfer (LET) of ions depends on the nuclide and velocity. Since LET value affects the mutation frequency, it is an important parameter to determine the most effective irradiation condition in mutagenesis. We determined the most effective dose in each LET for mutation induction in imbibed rice seeds. Subsequently, we analysed the mutated DNA responsible for the phenotype in morphological mutants. Most of the mutations were small deletions of less than 100 bp. Irradiations of C-ions and Ne-ions are effective for plant breeding because of the very high mutation rate and sufficient energy to disrupt a single gene. On the other hand, all mutations induced by Ar-ion (290 keV/μm) irradiation were large deletions ranging from 176 bp to approximately 620 kb. The average number of mutations in the target exon regions was 7.3, 8.5 and 4.3 per M3 mutant plant in C-ions, Ne-ions and Ar-ions, respectively. The number of mutations induced by heavy-ion irradiation was relatively small. We could identify six responsible genes for eight mutants induced by C-ion and Ne-ion irradiations and two responsible genes for four mutants induced by Ar-ion irradiation. Three of these were genes not previously described