B cell-derived GABA elicits IL-10⁺ macrophages to limit anti-tumour immunity

GABAを標的とする抗腫瘍免疫機構 --代謝産物を介した免疫細胞間制御の一端を解明--. 京都大学プレスリリース. 2021-11-10.Small, soluble metabolites not only are essential intermediates in intracellular biochemical processes, but can also influence neighbouring cells when released into the extracellular milieu1-3. Here we identify the metabolite and neurotransmitter GABA as a candidate signalling molecule synthesized and secreted by activated B cells and plasma cells. We show that B cell-derived GABA promotes monocyte differentiation into anti-inflammatory macrophages that secrete interleukin-10 and inhibit CD8⁺ T cell killer function. In mice, B cell deficiency or B cell-specific inactivation of the GABA-generating enzyme GAD67 enhances anti-tumour responses. Our study reveals that, in addition to cytokines and membrane proteins, small metabolites derived from B-lineage cells have immunoregulatory functions, which may be pharmaceutical targets allowing fine-tuning of immune responses

Prevalence and correlation of multiple chemical sensitivity and electromagnetic hypersensitivity with age, sex, and depression in the Japanese population: a retrospective study

Abstract Background In Japan, there are currently no definitive conclusions regarding the characteristics of multiple chemical sensitivity (MCS) and electromagnetic hypersensitivity (EHS). This study aimed to determine the prevalence and correlation of MCS and EHS with age, sex, and depression in the Japanese population. Methods An anonymous self-report questionnaire was distributed to 2,007 participants. Variables such as MCS, EHS, depression score, and demographic characteristics were individually evaluated using the U-test, chi-squared test, and correlation analyses. Moreover, we performed a covariance structure analysis to build a structural equation model. Results Older individuals and women were more likely to exhibit MCS and EHS symptoms. Moreover, depression was correlated with MCS and EHS. Conclusions Although MCS and EHS are strongly correlated, they exhibit distinct characteristics and symptoms, indicating that they can be regarded as separate conditions

New criteria for multiple chemical sensitivity based on the Quick Environmental Exposure and Sensitivity Inventory developed in response to rapid changes in ongoing chemical exposures among Japanese.

Background & objectivesThe Quick Environmental Exposure and Sensitivity Inventory (QEESI) developed by Miller and Prihoda in the USA is used as a questionnaire for patients with multiple chemical sensitivity (MCS) in >10 countries. We developed a Japanese version of QEESI, assessed its reliability and validity, and defined original cut-off values for screening Japanese patients with MCS in 2003. Our recent study revealed that opportunities for exposure to various chemicals had increased for people in Japan, while subjective symptoms of MCS in patients had increased in severity. In this study, we considered new cut-off values that combined QEESI subscale scores based on the current situation in Japan.MethodsThe questionnaire used was a Japanese version of QEESI. The survey was conducted from 2012 to 2015. Participants were 111 patients with MCS (mean age: 46 ± 20, 81% female) initially diagnosed by physicians, and 444 age- and gender-matched controls not diagnosed with MCS by doctors. The discriminatory validity of QEESI scores of patients and controls were evaluated by logistic regression and receiver operating characteristic analyses when considering interactions of the Masking Index (ongoing chemical exposure). New combined cut-off values were then set.ResultsNew combined cut-off values (meeting conditions of Chemical Intolerances ≥ 30, Symptom Severity ≥ 13, and Life Impacts ≥ 17) showed high sensitivity (82.0%) and specificity (94.4%). Using new criteria when considering ongoing chemical exposure, study participants were categorized as: Very suggestive, Somewhat suggestive, Problematic, and Not suggestive. Participants classified as Very suggestive included 25 (5.6%) controls.ConclusionsWe have set new criteria with combined cut-off values based on current Japanese conditions. Such new criteria can be used for screening and as a diagnostic aid for Japanese patients with MCS and suggest approximately 6% of the Japanese general population may be classified as "Very suggestive people with MCS"

Comparison of environmental intolerances and symptoms between patients with multiple chemical sensitivity, subjects with self-reported electromagnetic hypersensitivity, patients with bronchial asthma, and the general population

Abstract Background Environmental hypersensitivity/intolerance is considered closely related to allergic diseases. To understand these conditions, the environmental intolerances and symptoms of patients with multiple chemical sensitivity (MCS), subjects with self-reported electromagnetic hypersensitivity (EHS), patients with bronchial asthma (BA), and the general population were compared using universal questionnaires. Methods A survey was conducted from 2012 to 2015. The subjects were categorized in four groups: 111 patients with physician-diagnosed MCS, 119 subjects with self-reported EHS, patients with 98 physician-diagnosed BA, and 619 controls from general population. The Quick Environmental Exposure and Sensitivity Inventory and EHS questionnaire were used. The differences between the questionnaire scores among the four groups were tested using logistic regression analyses adjusted for age and gender as covariates. Results The MCS and EHS groups had significantly high scores of intolerances to multiple environmental factors, life impact, and multiple symptoms than the BA and control groups. Although the differences between most of these scores of the MCS and EHS groups were not significant, the electromagnetic hypersensitivity reaction was significantly higher in the EHS group than in the MCS group. In addition, the scores for intolerances to chemicals and other compounds, life impact, and several symptoms of the BA group were significantly higher than those of the control group. Conclusions This study clarified the similarities and differences of the environmental intolerances and symptoms between the four groups

The importance of bacterial and viral infections associated with adult asthma exacerbations in clinical practice.

Viral infection is one of the risk factors for asthma exacerbation. However, which pathogens are related to asthma exacerbation in adults remains unclear.The relation between various infections and adult asthma exacerbations was investigated in clinical practice.The study subjects included 50 adult inpatients due to asthma exacerbations and 20 stable outpatients for comparison. The pathogens from a nasopharyngeal swab were measured by multiplex PCR analysis.Asthma exacerbations occurred after a common cold in 48 inpatients. The numbers of patients with viral, bacterial, or both infections were 16, 9, and 9, respectively. The dominant viruses were rhinoviruses, respiratory syncytial virus, influenza virus, and metapneumovirus. The major bacteria were S. pneumoniae and H. influenzae. Compared to pathogen-free patients, the patients with pathogens were older and non-atopic and had later onset of disease, lower FeNO levels, lower IgE titers, and a higher incidence of comorbid sinusitis, COPD, or pneumonia. Compared to stable outpatients, asthma exacerbation inpatients had a higher incidence of smoking and comorbid sinusitis, COPD, or pneumonia. Viruses were detected in 50% of stable outpatients, but a higher incidence of rhinovirus, respiratory syncytial virus, and metapneumovirus infections was observed in asthma exacerbation inpatients. H. influenzae was observed in stable asthmatic patients. Other bacteria, especially S. pneumoniae, were important in asthma exacerbation inpatients.Viral or bacterial infections were observed in 70% of inpatients with an asthma exacerbation in clinical practice. Infection with S. pneumoniae was related to adult asthma exacerbation