Lactobacillus helveticus SBT2171 Attenuates Experimental Autoimmune Encephalomyelitis in Mice

We recently reported that Lactobacillus helveticus SBT2171 (LH2171) inhibited the proliferation and inflammatory cytokine production of primary immune cells in vitro, and alleviated collagen-induced arthritis (CIA) in mice, a model of human rheumatoid arthritis (RA). In this study, we newly investigated whether LH2171 could relieve the severity of experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS), which is an autoimmune disease, but develop the symptoms by different mechanisms from RA. In MS and EAE, main cause of the disease is the abnormality in CD4+ T cell immunity, whereas in RA and CIA, is that in antibody-mediated immunity. The intraperitoneal administration of LH2171 significantly decreased the incidence and clinical score of EAE in mice. LH2171 also reduced the numbers of pathogenic immune cells, especially Th17 cells, in the spinal cord at the peak stage of disease severity. Interestingly, before the onset of EAE, LH2171 administration remarkably decreased the ratio of Th17 cells to CD4+ T cells in the inguinal lymph nodes (LNs), where pathogenic immune cells are activated to infiltrate the central nervous system, including the spinal cord. Furthermore, the expression of interleukin (IL)-6, an inflammatory cytokine essential for Th17 differentiation, decreased in the LNs of LH2171-administered mice. Moreover, LH2171 significantly inhibited IL-6 production in vitro from both DC2.4 and RAW264.7 cells, model cell lines of antigen-presenting cells. These findings suggest that LH2171 might down-regulate IL-6 production and the subsequent Th17 differentiation and spinal cord infiltration, consequently alleviating EAE symptoms

Development of an adaptation scale for university students with developmental disorders (including the tendency): Extraction of the items

We developed an adaptation scale for university students with developmental disorders. 1) Subjects comprised 62 university students with developmental disorders (including tendency) who consulted the health support room at University A from April, 2010 to April, 2015. We obtained data regarding issues and situations reported by the students themselves. 2) We obtained data regarding issues reported by university staff. 3) We retrospectively examined behavioral problems and psychiatric symptoms. On the basis these data, we made the adaptation scale. The tool which evaluates the annoyance in the campus life, psychiatric symptoms, coping behavior, and social support is useful for 1) integrated evaluation, 2) common understanding of the supporters, 3) visualization of difficult concepts, and 4) grasping of the change

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Preventive Effect of Lactobacillus helveticus SBT2171 on Collagen-Induced Arthritis in Mice

We recently reported that the intraperitoneal inoculation of Lactobacillus helveticus SBT2171 inhibited the development of collagen-induced arthritis (CIA), a murine model of rheumatoid arthritis (RA). In the present study, we evaluated the effect of the oral administration of L. helveticus SBT2171 on CIA development and on the regulation of antigen-specific antibody production and inflammatory immune cells, which have been implicated in the development of RA. Both oral administration and intraperitoneal inoculation of L. helveticus SBT2171 reduced joint swelling, body weight loss, and the serum level of bovine type II collagen (CII)-specific antibodies in the CIA mouse model. The intraperitoneal inoculation also decreased the arthritis incidence, joint damage, and serum level of interleukin (IL)-6. In addition, the numbers of total immune cells, total B cells, germinal center B cells, and CD4+ T cells in the draining lymph nodes were decreased following intraperitoneal inoculation of L. helveticus SBT2171. These findings demonstrate the ability of L. helveticus SBT2171 to downregulate the abundance of immune cells and the subsequent production of CII-specific antibodies and IL-6, thereby suppressing the CIA symptoms, indicating its potential for use in the prevention of RA

Useful DNA typing using AmpFlSTR® Identifiler® Kit for formaldehyde-fixed paraffin-embedded (FFPE) tissues in early gastric cancer patient with lymph node metastasis

After distal gastrectomy in a patient with early gastric cancer, 27 regional lymph nodes around the stomach were evaluated for the existence of metastasis. There was a 0IIa+IIc type tumor 2.0x1.5cm in size in the gastric angle of the lesser curvature according to the Japanese Classification of Gastric Carcinoma (JCGC). Histologically, the lesion extended no deeper than the muscularis mucosae. The cancer stage was so early that no metastasis was expected to occur but a lymph node with metastasis was found in one lymph node along the common anterior hepatic artery (station No.8a). This histological type was a little different from that of a primary tumor. The doctor began to suspect that the lymph node with metastasis might have been from another patient by mistake. Therefore, DNA typing using the AmpFlSTR® Identifiler® kit was performed in formaldehyde-fixed paraffin-embedded (FFPE) tissues: 2 parts of gastric mucosa without cancer, one part of gastric mucosa with cancer, 4 lymph nodes without metastasis, and the lymph node station No.8a with metastasis. STR typing was successful in 6~14 STR loci and amelogenin gene, and the detected STR type was the same in all samples. Compared with the STR type using DNA from the patient’s blood, the lymph node station No.8a was from the same patient. The lymph node with metastasis turned out to be not from another patient. Therefore, we suggest that DNA typing using the AmpFlSTR® Identifiler® Kit for FFPE samples is useful in such clinical cases

Molecular and biological analysis revealed genetic diversity and high virulence strain of Toxoplasma gondii in Japan.

Toxoplasma gondii is classified into 16 haplogroups based on a worldwide genotyping study of the parasite. However, only a few isolates from Japan were included in this analysis. To conduct more precise genotyping of T. gondii, we examined the genotypes of Japanese isolates in this study. DNA sequences of 6 loci were determined in 17 Japanese isolates and compared with those of strains of 16 haplogroups. As a result, Japanese isolates were classified into four groups. We investigated the virulence of some Japanese isolates and found a highly virulent strain in mice, comparable to that of RH strain, although this Japanese isolate was sister to strains of haplogroup 2, which show moderate virulence in mice. We further investigated whether this high virulence isolate had different virulence mechanism and strategy to adapt to Japanese host from other strains by comparing the virulence-related genes, ROP5, 18 and the immunomodulatory gene, ROP16 of the isolate with those of archetypical strains (GT1, ME49 and VEG). This analysis indicated the high virulence of the isolate in mice was partly explained by gene sequences of ROP5 and ROP16. These findings lead to the elucidation of biodiversity of T. gondii and have potential to optimize the diagnostic protocol