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Systemic lupus erythematosus (SLE) is an autoimmune disease that involves multiple immune cell subsets. We analyzed immune cell subsets in human peripheral blood mononuclear cells (PBMC) in order to identify the cells that are significantly associated with SLE disease activity and treatment. The frequencies of various subsets of CD4+ T cells, B cells, monocytes and NK cells in PBMC were assessed in 30 healthy controls (HC), 30 rheumatoid arthritis (RA) patients and 26 SLE patients using flow cytometry. The correlations between subset frequencies in SLE and clinical traits including Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) were examined. Changes in subset frequencies after the treatment in SLE patients were investigated. We focused on CD25+LAG3+ T cells and investigated their characteristics, including cytokine secretion, mRNA expression and suppression capacity. We assessed correlations between CD25+LAG3+ T cells and SLEDAI by Spearman's rank correlation coefficient. CD25+LAG3+ T cells were significantly increased in SLE whereas there were few in RA and HC groups. CD25+LAG3+ T cell frequencies were significantly correlated with SLEDAI and were increased in patients with a high SLEDAI score (> 10). CD25+LAG3+ T cells produced both IL-17 and FOXP3, expressed mRNA of both FOXP3 and RORC and lacked suppressive capacity. CD25+LAG3+ T cells were associated with disease activity of SLE. CD25+LAG3+ T cells had features of both CD25+FOXP3+ regulatory T cells (CD25+ Treg) and Th17. CD25+LAG3+ T cells could be associated with the inflammatory pathophysiology of SLE. [ABSTRACT FROM AUTHOR]

IL-10-producing regulatory T cells (IL-10-producing Tregs) are one of the regulatory T cell subsets characterized by the production of high amounts of IL-10, the lack of FOXP3 expression and the strong immunosuppressive capabilities. IL-10-producing Tregs have been primarily reported as induced populations thus far, in part because identifying naturally occurring IL-10-producing Tregs was difficult due to the lack of definitive surface markers. Lymphocyte-activation gene 3 (LAG3) is a CD4 homologue that we have identified as being expressed on IL-10 producing Tregs. In human PBMC, LAG3 combined with CD49b efficiently identifies IL-10-producing Tregs. However, naturally occurring IL-10-producing Tregs in human secondary lymphoid tissue have not been described. In this report, we identified CD4 + CD25 − LAG3 + T cells in human tonsil. This T cell subset produced high amounts of IL-10 and expressed low levels of FOXP3. Surface markers and microarray analysis revealed that this is a distinct tonsillar CD4 + T cell subset. CD4 + CD25 − LAG3 + T cells expressed interleukin 10 (IL10), PR/SET domain 1 (PRDM1), and CD274 at high levels and chemokine receptor 5 (CXCR5) at low levels. CD4 + CD25 − LAG3 + T cells suppressed antibody production more efficiently than CD4 + CD25 + T cells, and CD4 + CD25 − LAG3 + T cells induced B cell apoptosis. Moreover, analysis of humanized mice revealed that this cell subset suppressed a graft-versus-host disease (GVHD) reaction in vivo . Our study reveals the existence of naturally occurring IL-10-producing Tregs in human secondary lymphoid tissue and their function in immune regulation. [ABSTRACT FROM AUTHOR]

Aim: The purpose of this study was to examine factors affecting depression trait among male intimate partner violence (IPV) victims in Japan utilizing a multiple linear regression analysis., Methods: A web-based questionnaire survey was conducted. Male IPV victims living in Japan were recruited to answer the questionnaire on the website on February 25-26, 2021. A total of 16,414 subjects were enrolled, of whom 1466 respondents were included in the study. Other than IPV exposure, information about sociodemographic characteristics, past traumatic experiences and psychiatric history was collected. The Domestic Violence Screening Inventory (DVSI), a 20-item questionnaire regarding IPV exposure, and the Patient Health Questionnaire-9 (PHQ-9) were used to determine the intensity and the type of IPV harm and to screen for depression, respectively., Results: The victims were more frequently subject to psychological abuse than to physical violence. Based on PHQ-9 scores, 10.7% of respondents exhibited moderate to severe depression. In the DVSI score, 79.2% of respondents required "observation and support." The lowest level of academic attainment (junior high school), positive psychiatric history, foregoing divorce to avoid adverse childhood experiences of their offspring, childhood exposure to domestic violence, younger age, having no children, and experience of school bullying were shown to be significantly associated with depression trait., Conclusion: Male IPV harm has a multilayered complexity. The sociodemographic characteristics and experiences of victims' own have a greater impact on depression trait than direct violent harm, suggesting that the violence-focused support might be inadequate for male victims. Comprehensive supports are urgently needed., Competing Interests: The authors declare no conflicts of interest., (© 2023 The authors. Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Systemic lupus erythematosus (SLE) is an autoimmune disease that involves multiple immune cell subsets. We analyzed immune cell subsets in human peripheral blood mononuclear cells (PBMC) in order to identify the cells that are significantly associated with SLE disease activity and treatment. The frequencies of various subsets of CD4 + T cells, B cells, monocytes and NK cells in PBMC were assessed in 30 healthy controls (HC), 30 rheumatoid arthritis (RA) patients and 26 SLE patients using flow cytometry. The correlations between subset frequencies in SLE and clinical traits including Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) were examined. Changes in subset frequencies after the treatment in SLE patients were investigated. We focused on CD25 + LAG3 + T cells and investigated their characteristics, including cytokine secretion, mRNA expression and suppression capacity. We assessed correlations between CD25 + LAG3 + T cells and SLEDAI by Spearman's rank correlation coefficient. CD25 + LAG3 + T cells were significantly increased in SLE whereas there were few in RA and HC groups. CD25 + LAG3 + T cell frequencies were significantly correlated with SLEDAI and were increased in patients with a high SLEDAI score (> 10). CD25 + LAG3 + T cells produced both IL-17 and FOXP3, expressed mRNA of both FOXP3 and RORC and lacked suppressive capacity. CD25 + LAG3 + T cells were associated with disease activity of SLE. CD25 + LAG3 + T cells had features of both CD25 + FOXP3 + regulatory T cells (CD25 + Treg) and Th17. CD25 + LAG3 + T cells could be associated with the inflammatory pathophysiology of SLE.

We analyzed the transcriptome of detailed CD4 + T cell subsets including them after abatacept treatment, and examined the difference among CD4 + T cell subsets and identified gene sets that are closely associated disease activity and abatacept treatment. Seven CD4 + T cell subsets (naive, Th1, Th17, Th1/17, nonTh1/17, Tfh and Treg) were sorted from PBMCs taken from 10 RA patients and 10 healthy controls, and three RA patients donated samples before and 6 months after abatacept treatment. Paired-end RNA sequencing was performed using HiSeq 2500. A total of 149 samples except for 12 outliers were analyzed. Overview of expression pattern of RA revealed that administration of abatacept exerts a large shift toward the expression pattern of HC. Most of differentially expressed gene (DEG) upregulated in RA (n = 1776) were downregulated with abatacept treatment (n = 1349). Inversely, most of DEG downregulated in RA (n = 1860) were upregulated with abatacept treatment (n = 1294). This DEG-based analysis revealed shared pathway changes in RA CD4 + T cell subsets. Knowledge-based pathway analysis revealed the upregulation of activation-related pathways in RA that was substantially ameliorated by abatacept. Weighted gene co-expression network analysis (WGCNA) evaluated CD4 + T cells collectively and identified a gene module that consisted of 227 genes and was correlated with DAS28-CRP (Spearman's rho = 0.46, p = 4 × 10 -9 ) and abatacept administration (Spearman's rho = -0.91, p = 5 × 10 -57 ). The most highly connected 30 genes of this module included ZAP70 and JAK3, and pathway analysis of this module revealed dysregulation of the TCR signaling pathway network, which was ameliorated by abatacept., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Regulatory T cells (Tregs) play a role in the suppression of inflammation in autoimmune diseases, and lymphocyte activation gene 3 (LAG3) was reported as a marker of interleukin (IL)-10-producing Tregs. We aimed to clarify the function of human IL-10-producing CD4 + CD25 - LAG3 + T cells (LAG3 + Tregs) and their association with rheumatoid arthritis (RA)., Methods: LAG3 + Tregs of human peripheral blood mononuclear cells (PBMCs) were cultured with B cells and follicular helper T cells to examine antibody suppression effects. The frequency of LAG3 + Tregs was evaluated in peripheral blood samples from 101 healthy donors and 85 patients with RA. In patients treated with abatacept, PBMC samples were analyzed before and after treatment. Naive CD4 + T cells were sorted and cultured in the presence of abatacept, followed by flow cytometric analysis and function assays., Results: LAG3 + Tregs produced high amounts of IL-10 and interferon-γ, and they suppressed B-cell antibody production more strongly than CD25 + Tregs. Cell-to-cell contact was required for the suppressive function of LAG3 + Tregs. The frequency of LAG3 + Tregs was lower in patients with RA, especially those with higher Clinical Disease Activity Index scores. LAG3 + Tregs significantly increased after 6 months of abatacept treatment, whereas CD25 + Tregs generally decreased. Abatacept treatment in vitro conferred LAG3 and EGR2 expression on naive CD4 + T cells, and abatacept-treated CD4 + T cells exhibited suppressive activity., Conclusions: IL-10-producing LAG3 + Tregs are associated with the immunopathology and therapeutic response in RA. LAG3 + Tregs may participate in a mechanism for the anti-inflammatory and immune-modulating effects of targeted therapy for costimulation.

Counseling for patients with cancer by a certified nurse in palliative care began in April 2011 in Minoh City Hospital. Counseling was provided immediately after a patient was informed by the treating physician of a primary diagnosis of cancer, a metastatic recurrence, or a decision to terminate cancer therapy. We examined the patient's support system after the counseling ended. The number of patients receiving end-of-life support with home or hospital care rapidly increased from 118 prior to the program's beginning to 186. The number of patients counseled was comparable to the rapid increase in their number(n=68). New cases in the outpatient department comprised 59% of all patients, of which, 45% began supportive counseling, with 43%of them ultimately returning home. Of the new cases receiving counseling in the hospital, 34%eventually returned home after discharge, and the highest percentage of discharges were to a palliative care unit or hospice program (48%). The initiation of counseling in the outpatient department allowed us to provide sufficient time to make decisions about appropriate places for end-of-life care. Cooperation with the patients' physicians was necessary to provide counseling from the outpatient department. Our findings suggest the importance of sharing the patients' medical and social information among the staff when necessary.