Elevated Apoptosis and Impaired Proliferation Contribute to Downregulated Peripheral γ

Objective. To investigate the frequency of peripheral γδ T cells in patients with systemic lupus erythematosus (SLE) and its correlation with disease activity and to analyze the apoptotic status, proliferation ability, and intracellular cytokine profile of these cells. Methods. Flow cytometry was performed to detect the percentage and intracellular cytokine expression of peripheral γδ T cells from SLE patients. Annexin-V/PI double staining was applied to determine the proportion of apoptotic γδ and CD3+ T cells. γδ T cell proliferation was analyzed by CFSE labeling technique. Results. The percentage and absolute number of γδ T cells were remarkably decreased in active SLE patients compared to those in inactive patients and healthy controls, with γδ T cell count negatively correlated with disease activity. Compared with healthy controls, peripheral γδ T cells from active SLE patients exhibited higher apoptotic rate and lower proliferation ability, as well as elevated expression of intracellular IFN-γ, IL-4, IL-10, and TGF-β, but not IL-17 or Foxp3. Conclusion. Decreased γδ T cells in the peripheral blood of SLE patients might be caused by upregulated apoptosis and downregulated cell proliferation. These γδ T cells may secret both pro- and anti-inflammatory cytokines to perform their functions in SLE

Rapidly progressive interstitial lung disease risk prediction in anti-MDA5 positive dermatomyositis: the CROSS model

BackgroundThe prognosis of anti-melanoma differentiation-associated gene 5 positive dermatomyositis (anti-MDA5+DM) is poor and heterogeneous. Rapidly progressive interstitial lung disease (RP-ILD) is these patients’ leading cause of death. We sought to develop prediction models for RP-ILD risk in anti-MDA5+DM patients.MethodsPatients with anti-MDA5+DM were enrolled in two cohorts: 170 patients from the southern region of Jiangsu province (discovery cohort) and 85 patients from the northern region of Jiangsu province (validation cohort). Cox proportional hazards models were used to identify risk factors of RP-ILD. RP-ILD risk prediction models were developed and validated by testing every independent prognostic risk factor derived from the Cox model.ResultsThere are no significant differences in baseline clinical parameters and prognosis between discovery and validation cohorts. Among all 255 anti-MDA5+DM patients, with a median follow-up of 12 months, the incidence of RP-ILD was 36.86%. Using the discovery cohort, four variables were included in the final risk prediction model for RP-ILD: C-reactive protein (CRP) levels, anti-Ro52 antibody positivity, short disease duration, and male sex. A point scoring system was used to classify anti-MDA5+DM patients into moderate, high, and very high risk of RP-ILD. After one-year follow-up, the incidence of RP-ILD in the very high risk group was 71.3% and 85.71%, significantly higher than those in the high-risk group (35.19%, 41.69%) and moderate-risk group (9.54%, 6.67%) in both cohorts.ConclusionsThe CROSS model is an easy-to-use prediction classification system for RP-ILD risk in anti-MDA5+DM patients. It has great application prospect in disease management

Roles of T Cells in the Pathogenesis of Autoimmune Diseases

γδ T cells are a minor population of T cells that express the TCR γδ chains, mainly distributed in the mucosal and epithelial tissue and accounting for less than 5% of the total T cells in the peripheral blood. By bridging innate and adaptive immunity, γδ T cells play important roles in the anti-infection, antitumor, and autoimmune responses. Previous research on γδ T cells was primarily concentrated on infectious diseases and tumors, whereas their functions in autoimmune diseases attracted much attention. In this paper, we summarized the various functions of γδ T cells in two prototypical autoimmune connective tissue diseases, that is, SLE and RA, elaborating on their antigen-presenting capacity, secretion of proinflammatory cytokines, immunomodulatory effects, and auxiliary function for B cells, which contribute to overproduction of proinflammatory cytokines and pathogenic autoantibodies, ultimately leading to the onset of these autoimmune diseases. Elucidation of the roles of γδ T cells in autoimmune diseases is not only conducive to in-depth understanding of the pathogenesis of these diseases, but also beneficial in providing theoretical support for the development of γδ T-cell-targeted therapy