Mammalian Target of Rapamycin Inhibitors Permit Regulatory T Cell Reconstitution and Inhibit Experimental Chronic Graft-versus-Host Disease

Chronic graft-versus-host disease (GVHD) remains a major late complication of allogeneic bone marrow transplantation (BMT). In a previous study, impaired thymic negative selection of the recipients permitted the emergence of pathogenic T cells that cause chronic GVHD using MHC class II-deficient (H2-Ab1 KO) B6 into OH model and CD4(+) T cells isolated from chronic GVHD mice caused chronic GVHD when administered into the secondary recipients. In this study, we evaluated the kinetics of regulatory T cell (Treg) reconstitution in wild type B6 into C3H model. After myeloablative conditioning, host Tregs disappeared rapidly, followed by expansion of Tregs derived from the donor splenic T cell inoculum. However, the donor splenic T cell derived Treg pool contracted gradually and was almost completely replaced by newly generated donor bone marrow (BM)-derived Tregs in the late post-transplantation period. Next, we compared the effects of cyclosporine (CSA) and mammalian target of rapamycin (mTOR) inhibitors on Treg reconstitution. Administration of CSA significantly impaired Treg reconstitution in the spleen and thymus. In contrast, BM-derived Treg reconstitution was not impaired in mTOR inhibitor-treated mice. Histopathological examination indicated that mice treated with GSA, but not mTOR inhibitors, showed pathogenic features of chronic GVHD on day 120. Mice treated with CSA until day 60, but not mTOR inhibitors, developed severe chronic GVHD followed by adoptive transfer of the pathogenic CD4(+) T cells isolated from H2-Ab1 KO into C3H model. These findings indicated that long-term use of CSA impairs reconstitution of BM-derived Tregs and increases the liability to chronic GVHD. The choice of immunosuppression, such as calcineurin inhibitor-free GVHD prophylaxis with mTOR inhibitor, may have important implications for the control of chronic GVHD after BMT

Perspective Chapter: Mountain Health Care Room

The Kinjo University Faculty of Nursing has been running a project since 2017 as part of its community collaboration activities to help Hakusanroku residents maintain good health. First, we opened the Mountain Health Care Room for community salon participants and conducted a basic survey of Hakusanroku healthcare supporters and community residents. We then provided health education and recreational activities to help older adults maintain good health. Since 2020, we have been unable to hold community activities due to the COVID-19 pandemic, and have been attempting to determine the day-to-day circumstances of residents. In addition to in-person community activities, there is a need for new initiatives such as online activities to help people connect and help older adults living in Hakusanroku to maintain good health

Synthetic retinoid Am80 ameliorates chronic graft-versus-host disease by down-regulating Th1 and Th17.

Chronic GVHD (cGVHD) is a main cause of late death and morbidity after allogeneic hematopoietic cell transplantation, but its pathogenesis remains unclear. We investigated the roles of Th subsets in cGVHD with the use of a well-defined mouse model of cGVHD. In this model, development of cGVHD was associated with up-regulated Th1, Th2, and Th17 responses. Th1 and Th2 responses were up-regulated early after BM transplantation, followed by a subsequent up-regulation of Th17 cells. Significantly greater numbers of Th17 cells were infiltrated in the lung and liver from allogeneic recipients than those from syngeneic recipients. We then evaluated the roles of Th1 and Th17 in cGVHD with the use of IFN-γ-deficient and IL-17-deficient mice as donors. Infusion of IFN-γ(-/-) or IL-17(-/-) T cells attenuated cGVHD in the skin and salivary glands. Am80, a potent synthetic retinoid, regulated both Th1 and Th17 responses as well as TGF-β expression in the skin, resulting in an attenuation of cutaneous cGVHD. These results suggest that Th1 and Th17 contribute to the development of cGVHD and that targeting Th1 and Th17 may therefore represent a promising therapeutic strategy for preventing and treating cGVHD

Role of Coherent Low-Frequency Motion in Excited-State Proton Transfer of Green Fluorescent Protein Studied by Time-Resolved Impulsive Stimulated Raman Spectroscopy

Green fluorescent protein (GFP) from jellyfish Aequorea victoria, an essential bioimaging tool, luminesces via excited-state proton transfer (ESPT) in which the phenolic proton of the <i>p</i>-hydroxybenzylideneimidazolinone chromophore is transferred to Glu222 through a hydrogen-bond network. In this process, the ESPT mediated by the low-frequency motion of the chromophore has been proposed. We address this issue using femtosecond time-resolved impulsive stimulated Raman spectroscopy. After coherently exciting low-frequency modes (<300 cm^–1) in the excited state of GFP, we examined the excited-state structural evolution and the ESPT dynamics within the dephasing time of the low-frequency vibration. A clear anharmonic vibrational coupling is found between one high-frequency mode of the chromophore (phenolic CH bend) and a low-frequency mode at ∼104 cm^–1. However, the data show that this low-frequency motion does not substantially affect the ESPT dynamics

Classification of Wheezing Children in Rural Bangladesh by Intensity of Ascaris Infection, Total and Specific IgE Levels, History of Pneumonia, and Other Risk Factors

Ascaris lumbricoides is the most common soil-transmitted helminth and infects 447 million people in impoverished areas worldwide. It causes serious morbidity including wheezing and influences various aspects of human immunity, such as type 2 innate lymphoid cells, regulatory T cell function, and acquired immunity. Thus, it is crucial to elucidate its influence on human immunity. We aimed to classify wheezing children based on their Ascaris infection intensity and other risk factors using hierarchical cluster analysis to determine the mechanisms of and the degree to which Ascaris contributes to childhood wheezing in rural Bangladesh. We analyzed relevant data collected in 2001. The participants included 219 5-year-old wheezing children who were randomly selected from 1705 children living in the Matlab Health and Demographic Surveillance area of the International Centre for Diarrhoeal Disease Research, Bangladesh. Hierarchical cluster analysis was conducted using variables of history of pneumonia, total and specific immunoglobulin E levels, Ascaris infection intensity, and parental asthma. Three distinct wheezing groups were identified. Children in Cluster 1 (n=50) had the highest titers of the total, anti-Ascaris, anti-Dermatophagoides pteronyssinus, and anticockroach IgEs and experienced the fewest episodes of pneumonia. Cluster 2 (n=114), the largest group, experienced few episodes of pneumonia and had the lowest titers of the total, anti-Ascaris, anti-Dp, and anticockroach IgEs. Cluster 3 (n=32) consisted of participants with the most episodes of pneumonia and lower titers of the total and specific IgEs. The extremely high prevalence of Ascaris infection found in Clusters 1-3 was 78%, 77%, and 72%, respectively. Childhood wheezing in rural Bangladesh could be divided into three groups, with 26% of wheezing attributable to anti-Ascaris IgE and 16% to history of pneumonia during early childhood, and 58% might have been due to Ascaris infection without elevated anti-Ascaris IgE

Organizational climate with gender equity and burnout among university academics in Japan

We investigated relationships between the perception of organizational climate with gender equity and psychological health among 94 women and 211 men in a Japanese private university in 2015 using the Copenhagen Burnout Inventory (i.e., personal, work-related and student-related burnout). Perceptions of organizational climate with respect to gender equity were measured with two scales including organizational engagement with a gender equal society in the workplace (consisting of three domains of 'Women utilization', 'Organizational promotion of gender equal society' and 'Consultation service'); and a gender inequality in academia scale that had been previously developed. Multivariable linear models demonstrated significant statistical interactions between gender and perceptions of organizational climate; 'Women utilization' or lack of 'Inequality in academia' alleviated burnout only in women. In consequence of this gender difference, when 'Women utilization' was at a lower level, both personal (p=.038) and work-related (p=.010) burnout scores were higher in women, and the student-related burnout score was lower in women when they perceived less inequality in academia than in men (p =.030). As such, it is suggested organizational fairness for gender equity may be a useful tool to help mitigate psychological burnout among women in academia

Organizational climate with gender equity and burnout among university academics in Japan

We investigated relationships between the perception of organizational climate with gender equity and psychological health among 94 women and 211 men in a Japanese private university in 2015 using the Copenhagen Burnout Inventory (i.e., personal, work-related and student-related burnout). Perceptions of organizational climate with respect to gender equity were measured with two scales including organizational engagement with a gender equal society in the workplace (consisting of three domains of 'Women utilization', 'Organizational promotion of gender equal society' and 'Consultation service'); and a gender inequality in academia scale that had been previously developed. Multivariable linear models demonstrated significant statistical interactions between gender and perceptions of organizational climate; 'Women utilization' or lack of 'Inequality in academia' alleviated burnout only in women. In consequence of this gender difference, when 'Women utilization' was at a lower level, both personal (p=.038) and work-related (p=.010) burnout scores were higher in women, and the student-related burnout score was lower in women when they perceived less inequality in academia than in men (p =.030). As such, it is suggested organizational fairness for gender equity may be a useful tool to help mitigate psychological burnout among women in academia