A cohort of highly activated CD99- CD72+ B cells promoting autoimmune progression in juvenile systemic lupus erythematosusFang, Chen, Xi
et alInt Immunopharmacol (2025) 152, 114466
Abstract: CD72 inhibits the development of systemic lupus erythematosus (SLE) by suppressing TLR7-dependent B cell responses to self-nucleic acids (NAs). The absence of CD72 promotes the progression of lupus disease. Here, we find a highly activated subset of CD99- CD72+ B cells (CD72+ BCs) expressing elevated levels of TLR7 in juvenile SLE, which contributes to autoimmunity. Through multi-omics integrated analysis of single-cell RNA sequencing(scRNA-seq) data and bulk RNA sequencing (RNA-seq) data, we demonstrate that CD72+ BCs possess characteristics of both activated naïve B cells (aN) and age-associated B cells (ABCs). Concurrently, CD72+ BCs exhibit pronounced plasmablast-like features compared to other cellular subpopulations. We propose a plausible conclusion that CD72+ BCs represent a critical transitional cell population involved in the activation and subsequent plasma cell differentiation of naïve B cells and age-related B cells following exposure to self-antigens in SLE. This finding offers novel opportunities for elucidating the genesis of autoantibody-secreting cells involved in the autoimmune response processes in lupus.Copyright © 2025 Elsevier B.V. All rights reserved.
Proteomic associations with fluctuation and long-term changes in BMI: A 40-year follow-up studyObeso, Drouard, Palviainen
et almedRxiv (2025)
Abstract: While some studies have explored associations between weight change and blood proteins, most have been intervention-based, offering limited insight into proteomic associations with long-term weight gain. It remains unclear whether plasma proteins are related to BMI fluctuation over time. This study investigates associations of long-term BMI changes and fluctuations with over 1,000 plasma proteins involved in cardiometabolic and inflammation functions.The study included 304 Finnish adult twins (117 men) born before 1958 from the Older Finnish Twin Cohort, with BMI data spanning five time points (1975, 1981, 1990, 2011, and 2012-2014). Proteomic data were derived from blood samples collected at the last BMI measurement. Linear mixed-effects models analyzed individual BMI trajectories, producing intercepts (baseline BMI) and slopes (BMI change rates). BMI fluctuation was calculated as the average squared deviation from expected BMI across time points. Associations between BMI changes/fluctuation and (i) 1,231 plasma proteins related to cardiometabolic and inflammatory functions and (ii) polygenic risk scores for BMI (PRSBMI), as well as interaction effects between PRSBMI and baseline BMI on protein-BMI relationships were studied. Within-pair analyses using monozygotic twins were conducted to account for shared confounding factors.A total of 135 proteins were associated with changes in BMI over 40 years, while 17 proteins were linked to fluctuation in BMI: 12 associations (10 with BMI changes and 2 with fluctuation) remained significant in within-twin pair analyses. PRSBMI associated with BMI changes but not with fluctuations. PRSBMI-protein interactions explaining BMI changes or fluctuation was found, though a single interaction between the CD72 protein and baseline BMI was observed.This study highlights significant associations between plasma proteins and long-term BMI changes and fluctuations, with no evidence of PRSBMI-protein interactions influencing BMI trends. These findings underscore the substantial role of environmental factors in shaping proteome-BMI associations over adulthood.
Soluble CD72 concurrently impairs T cell functions while enhances inflammatory response in sepsisYang, Ma, Feng
et alInt Immunopharmacol (2025) 147, 113981
Abstract: Sepsis is defined as multi-organ dysfunction caused by dysregulated host response to infection. This dysregulated host response includes enhanced inflammatory responses and suppressed adaptive immunity, but the molecular mechanisms behind it have not yet been elucidated. CD72, a type II transmembrane protein that is primarily expressed in B cells, was found to play an immunomodulatory role in the immune system and was associated with mortality in patients with sepsis. However, whether CD72 affects the pathogenesis of sepsis by influencing the immune response remains unclear.We first collected peripheral blood from 40 healthy volunteers and 57 septic patients and analyzed the mRNA levels of CD72 and the expression of its soluble form sCD72 using Realtime-PCR and ELISA. We then employed the CRISPR/Cas9 system to generate CD72 knockout mice (CD72-KO) and established a cecal ligation and puncture (CLP) model to analyze the effects of CD72 gene deletion on the survival, organ injury and immune response of septic mice by Kaplan-Meier survival analysis, pathological sections and flow cytometry. We also observe the effects of excess sCD72 on survival and immune response in sepsis by injecting recombinant CD72 protein into mice. Finally, the mechanism of sCD72 affecting sepsis immunity was analyzed by fluorescence staining, confocal microscopy and flow cytometry.We found that when sepsis occurs, the levels of CD72 mRNA and cell surface CD72 in immune cells decrease, while the level of soluble sCD72 in the blood increases significantly. Excessive sCD72 increased sepsis mortality in a dose-dependent manner, which can bind to CD100 on the surface of T cells and enter the cytoplasm, leading to impaired T cell functions, including a decrease in CD4+IFN-γ+, CD8+Perforin+, CD8+GZMB+, and CD8+FASL+ population and an increase in inflammatory CD4+TNF-α+ population, thereby suppressing adaptive immunity while enhancing inflammatory response.The immunosuppression of sepsis has been recognized, but the underlying mechanism has not been fully elucidated. Our study identified for the first time that sCD72 is an important mediator that cause adaptive immunosuppression during sepsis, which leads to T cell suppression by competitively binding to CD100 on the surface of T cells. Our study provides novel insights in our understanding of sepsis-related immunosuppression and may provide translational opportunities for the design of new diagnostic biomarkers and therapeutic targets for sepsis.Copyright © 2024 Elsevier B.V. All rights reserved.
Intermittent fasting reduces inflammation and joint damage in a murine model of rheumatoid arthritis: insights from transcriptomic and metagenomic analysesCuevas-Martínez, González-Chávez, Bermúdez
et alBMC Rheumatol (2024) 8 (1), 64
Abstract: Intermittent fasting (IF) has shown benefits in various pathological conditions. Although its anti-inflammatory potential has been recognized, its effects on the mechanism underlying rheumatoid arthritis (RA) remain insufficiently characterized. This study aimed to investigate the effects of IF in a murine model of RA.Collagen-induced arthritis (CIA) was developed in sixteen male DBA/1 mice, randomly assigned to two groups, with one undergoing IF every other day for four weeks. The effects of IF on joint inflammation and remodeling were evaluated clinically, histologically, and through tomography. Transcriptomic changes were characterized using expression microarrays, validated by RT-qPCR, and confirmed by immunohistochemistry. Additionally, modifications in gut microbiota were assessed through 16 S sequencing.Mice subjected to IF significantly reduced the incidence and severity of clinical arthritis. Histological and radiographic assessments confirmed a decrease in inflammation and joint damage. Transcriptomic analysis revealed that IF led to the upregulation of 364 genes and the downregulation of 543 genes, with notable reductions in inflammatory signaling pathways associated with RA-related genes, including Cd72, Cd79a, Ifna, Il33, and Bglap 2. Notably, IL33 emerged as a pivotal mediator in the inflammatory processes mitigated by fasting. Key regulators associated with IF effects, such as CEBPA, FOXO1, HIF1A, PPARG, and PPARA, were identified, indicating a complex interplay between metabolic and inflammatory pathways. Furthermore, differential expression of microRNAs and lncRNAs, including miR-15b, miR-103-2, miR-302a, miR-6985, and miR- 5624, was observed. Metagenomic analysis indicated that IF enhanced the abundance and diversity of the gut microbiome, explicitly promoting anti-inflammatory bacterial populations, notably within the genus Ruminococcaceae.Our findings suggest that IF exerts significant anti-inflammatory and immunoregulatory effects in the context of CIA. Given its non-risky nature, further investigation into the potential benefits of IF in patients with RA is warranted.Not applicable.© 2024. The Author(s).
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