Immunologic Research最新文献

Immunoglobulin G4-related disease (IgG4-RD) is a rare immune-mediated fibro-inflammatory condition that can affect nearly any organ, with breast involvement (IgG4-related sclerosing mastitis, IgG4-RM) being exceptionally uncommon. This disease primarily affects middle-aged to elderly women and is frequently misdiagnosed as malignancy due to non-specific clinical and imaging features. We report a case of a 44-year-old woman with a painless right breast mass showing hypoechoic ultrasound findings and magnetic resonance imaging (MRI) characteristics, including a high ADC value and homogeneous enhancement with a persistent time-intensity curve (TIC). Histopathology confirmed IgG4-RM, with no recurrence after 12 months. A review of 24 published lectures highlights the diagnostic challenges and imaging variability of IgG4-RM.

To evaluate the therapeutic effectiveness of belimumab (BLM) in childhood systemic lupus erythematosus (cSLE) by analyzing peripheral blood Breg cell subsets and related cytokines at multiple time points post-treatment, compared with conventional therapy. From January 2023 to August 2023, 36 cSLE patients receiving BLM plus standard therapy (BLM group) and 35 receiving standard therapy alone (conventional group) were enrolled. Thirty age- and sex-matched healthy children were included as controls. Flow cytometry was used to detect absolute counts and ratios of peripheral Breg cell subsets at baseline, 6 weeks, 6 months, and 1 year. Serum cytokine levels (IL-2, IL-10, IL-21, IL-35, and IFN-γ) were measured by ELISA. After 6 weeks, IL-2, IL-21, and IFN-γ levels decreased significantly in both groups (P > 0.05 between groups); however, after 6 months and 1 year, these cytokines remained lower in the BLM group (all P < 0.05). IL-10 and IL-35 levels increased in both groups from week 6, with a milder increase in the BLM group (all P < 0.05). CD3⁻CD19⁺ B cells declined in both groups, with significant intergroup differences (P < 0.001). The BLM group showed a higher proportion of CD27⁺CD24⁺ B cells at week 6 compared to the conventional group (P < 0.05), but this reversed at 1 year (P < 0.05). CD38⁺CD24⁺ B cells were significantly higher in the BLM group at 6 months and 1 year (P < 0.001), while the conventional group showed no significant change after 6 weeks (P > 0.05). At baseline, the relative proportion of CD38⁺CD19⁺ B cells was higher in the BLM group than in the conventional treatment group (all P < 0.05). With ongoing treatment, both groups showed a decreasing trend in B cell proportions, with statistically significant differences observed within each group (all P < 0.05). Moreover, the decline in the BLM group was more pronounced compared to the conventional group at corresponding time points (all P < 0.05). Belimumab may exert immunomodulatory effects in childhood systemic lupus erythematosus by influencing peripheral Breg cell subsets and cytokine profiles. Compared with conventional therapy, it appears to provide more sustained regulation of certain immune parameters over time. These findings suggest its potential as a complementary therapeutic option targeting B cell dysregulation in cSLE, although further studies are needed to confirm these observations and clarify the underlying mechanisms.

Abnormal galactosylation of IgA is a core factor in the development of IgA nephropathy (IgAN). Suppressor of cytokine signaling 1 (SOCS1) expression negatively correlates with IgA1 secretion in IgAN patients and that TLR9/MyD88 promotes aberrantly glycosylated IgA formation. Therefore, the present study exposed whether SOCS1 is involved in aberrant galactosylation of IgA in IgAN by regulating the TLR9/MyD88 signaling pathway through in vivo and in vitro experiments. Differential expression of SOSC1 in IgAN patients and non-IgAN patients was analyzed using bioinformatics analysis and immunofluorescence. The IgAN mouse model and the IgA1-secreting DAKIKI cell model were used to validate the effect of SOCS1 on aberrant IgA galactosylation in IgAN. In addition, qRT-PCR, western blot, and immunohistochemistry experiments were performed to reveal the regulation of the TLR9/MyD88 pathway by SOCS1 in IgAN. The expression of SOCS1 was suppressed in renal tissues and peripheral blood mononuclear cells (PBMC) of IgAN patients, consistent with the results of dataset GSE35487. The expression of C1GALT1 in PBMC from IgAN patients was decreased and positively correlated with SOCS1 expression, while the expressions of TLR9 and MyD88 were increased and negatively correlated with SOCS1 expression. In vitro, SOCS1 overexpression inhibited the secretion of IgA1 and galactose-deficient IgA1 (Gd-IgA1) in DAKIKI cells, as well as the expression of TLR9. Knockdown of SOCS1 had the opposite effect. As a negative regulator of TLR9, SOCS1 inhibited the expression of TLR9, thereby preventing aberrant IgA galactosylation. MyD88 knockdown restored the CpG-ODN (TLR9 ligand)-induced overproduction of IgA1 and Gd-IgA1, and the reduction of C1GALT1. In vivo experiments demonstrated that SOCS1 significantly inhibited the production of aberrant glycosylated IgA IgG-IgA immune complexes and IL-6 in mice, reduced glomerular IgA, IgG, and C3 deposition and tethered cell proliferation, and alleviated renal injury. Decreased expression of SOCS1 contributes to IgAN pathogenesis by promoting aberrant IgA galactosylation via activating TLR9/MyD88 pathway. Our study may provide a prospective treatment target for IgAN.

Atopic dermatitis (AD) is a chronic inflammatory skin disease resulting from complex interactions between genetic, environmental, and immunological factors, particularly the dysregulation of T helper (Th) cell subsets. While Th2 responses have been central to AD research, evidence highlights the role of Th9 cells and their signature cytokine, interleukin-9 (IL-9), in allergic inflammation. However, the involvement of the Th9/IL-9 axis in AD remains insufficiently characterized. This study investigates the role of the Th9/IL-9 axis in AD through an integrated clinical, immunological, and molecular approach. The study comprised a total of 89 subjects, consisting of 54 AD cases and 35 healthy controls. Disease severity and allergen sensitivity were assessed using SCORAD scores and skin prick testing, respectively. PU-1 mRNA was quantified using real-time PCR. Th9 cell frequency was determined through flow cytometry, vitamin D levels were measured by chemiluminescence, and total IgE and IL-9 levels were estimated using ELISA. AD patients demonstrated a significant increase in circulating Th9 cell frequency (11.5 ± 0.3% vs. 5.0 ± 0.5%, p < 0.0001), PU.1 mRNA expression with an average 2.5-fold upregulation (p < 0.001), and elevated serum IL-9 concentrations (18.6 ± 6.3 pg/mL vs. 8.3 ± 1.9 pg/mL, p < 0.0001) compared to healthy controls. Stratified analysis revealed significant associations of PU.1 mRNA and IL-9 levels with rural residence, vitamin D deficiency, and peripheral eosinophilia (p < 0.05). Allergen sensitivity, as determined by skin prick testing, was positive in 50% of AD patients, and 66.7% exhibited elevated total serum IgE levels. Our findings underscore the involvement of the Th9/PU.1/IL-9 axis in the immunopathogenesis of AD. The observed upregulation of Th9 cell frequency, PU.1 expression, and IL-9 levels suggests a contributory role of Th9-mediated pathways in disease development and severity. These results provide a foundation for future studies investigating the dynamic crosstalk between Th9 cells, other immune cell subsets, and epidermal components, with the aim of identifying novel immunomodulatory targets for precision therapy in AD.

STING-associated vasculopathy with onset in infancy (SAVI) is a very rare autosomal-dominant Mendelian autoinflammatory disease caused by heterozygous gain-of-function mutations in STING1. Reported carriers of a STING1 gain-of-function mutations are mostly symptomatic. Herein, we present a case study of an infant who presented with cyanosis, dyspnea, clubbing fingers, failure to thrive, and widespread interstitial changes, all consistent with interstitial lung disease (ILD); however, there was a notable lack of characteristic cutaneous features and recurrent fever. Whole-exome sequencing detected a pathogenic heterozygous mutation (p.Arg218Gln) in STING1. Intriguingly, this mutation was also present in her father (aged 32 years), whereas this carrier was healthy and without clinical symptoms. This study emphasizes the need to consider the possibility of SAVI in infants with ILD, even if they lack typical manifestations. Our study also underlines the possibility that carriers with STING gain-of-function mutations are clinically asymptomatic.

Basement membranes (BMs) and tumor-associated macrophages (TAMs) are crucial stromal components in pancreatic cancer (PC), critically influencing disease progression. Bulk and single-cell RNA-seq (scRNA-seq) data were acquired from publicly available databases. Through integration of multiple machine learning algorithms, we developed and validated a BM-related subtype and prognostic signature in PC cohorts. The expression profiles of BM-related genes in PC were verified using experimental approaches. We further investigated the functional mechanisms of a core gene in PC progression. Additionally, we characterized the TAM landscape in PC, revealing distinct TAM subsets associated with tumor progression and their dynamic interactions with BM components. Based on BM-related gene expression profiles, PC samples were stratified into two distinct subtypes. Our integrated prognostic signature combining LASSO and survival-SVM algorithms demonstrated robust performance in predicting PC outcomes and clinical characteristics. LAMA3, ITGA3, and ITGB6 showed higher expression in PC specimens versus normal controls. Functional experiments confirmed that ITGB6 knockdown markedly suppressed PC progression. Through integrative analysis of multiple scRNA-seq datasets of PC, we established a single-cell landscape of TAMs and ductal cells, respectively. SPP1 + TAMs correlated with poor PC prognosis and facilitated tumor progression through ITGB6-mediated interactions. In this study, we established novel PC subtypes and constructed a prognostic signature based on BM-related genes. An atlas of TAMs was constructed in PC. SPP1 + macrophages drove pancreatic cancer progression via ITGB6-mediated interactions.

Discogenic low back pain (DLBP) is one of the main causes of chronic low back pain, and its core pathological mechanism is due to various molecular changes caused by intervertebral disc degeneration. The normal intervertebral disc is composed of the nucleus pulposus, annulus fibrosus, and cartilaginous endplate, and has structural characteristics without blood vessels or nerves, relying on dispersed support to maintain homeostasis. During the process of degeneration, nucleus pulposus cells undergo apoptosis and cell senescence, its synthesis ability decreases, and the balance of extracellular matrix (ECM) is disrupted. Meanwhile, inflammatory factors such as IL-1β and TNF-α are continuously upregulated, activating pathways such as NF-κB and MAPK, inducing the expression of MMPs and ADAMTS, and accelerating ECM degradation. Matrix disruption further promotes the release of neurotrophic factors (such as NGF, VEGF), induces angiogenesis and nerve fiber invasion into the nucleus pulposus area, destroys the immune barrier, and leads to peripheral nerve sensitization. The central system mediates central remodeling through factors such as BDNF and CGRP, maintaining and amplifying pain signals. This article systematically summarizes the molecular mechanism of DLBP and summarizes relevant treatment strategies based on it, including conservative treatments such as NSAIDs, interventional methods such as radiofrequency ablation and fusion, as well as emerging therapies such as targeted anti-inflammatory, anti-neurogenic, matrix protection, and stem cell regeneration. The aim is to provide theoretical support and research directions for personalized treatment and mechanism interventions of DLBP.

Chronic inflammation underlies many diseases, posing challenges in therapeutic management due to the limitations and side effects of current treatments and necessitating novel therapeutic solutions. Here, we introduce PS77, a novel α-helical peptide derived from Squama Manitis, a Traditional Chinese Medicine, and unveil its remarkable anti-inflammatory properties, potentially revolutionizing biomaterials design for targeted anti-inflammatory therapies. An in vitro TNF-α-induced inflammatory model in human keratinocytes (HaCaT cells) was used to demonstrate PS77's significant impact. We demonstrated that PS77 significantly reduced IL-8 and MMP-3 expression, indicating potent anti-inflammatory activity without cytotoxicity to normal cells. Transcriptomic analysis further elucidated PS77's mechanism of action, revealing significant modulation of 265 genes (137 upregulated and 128 downregulated), with a particular focus on the downregulation of genes within the BMP and TGF-β signaling pathways-key players in inflammation. Moreover, PS77 regulated several inflammation-associated genes, including CHRNA7, CXCR5, RXRG, KRT76, IL12RB2, and COLEC11, underscoring its comprehensive anti-inflammatory effects. This study not only highlights PS77's therapeutic potential as a biomaterial for treating inflammatory diseases but also paves the way for further research into its mechanisms and applications in biomedicine. By leveraging the novel biomaterial properties of PS77, this research may contribute to the development of targeted and efficient anti-inflammatory therapies, marking a significant advance in the field of biomaterials and offering a promising avenue for inflammation management.

Allergic asthma is a chronic inflammatory disease of the airways. The objective of this study was to identify potential therapeutic targets for allergic asthma through RNA sequencing (RNA-seq) and experimental analyses. Allergic asthma models, both in cells and mice, were induced using house dust mite (HDM) treatment. RNA-seq analysis of lung tissues from HDM-induced allergic asthma mice and control mice was performed to identify differentially expressed genes (DEGs), and functional enrichment analysis of DEGs was performed. Spon2 knockdown was achieved via siRNA transfection and adeno-associated virus transduction. Bronchoalveolar lavage fluid (BALF) from mice was analyzed using cytology, ELISA for cytokines, and Giemsa staining. Lung tissues underwent HE staining, immunohistochemical staining, and Masson staining. Key gene expression levels were monitored in cellular and mouse models using real-time quantitative PCR and western blotting. RNA-seq and histological analysis of the HDM-induced allergic asthma mouse model revealed increased macrophage infiltration and upregulation of Spon2 in the lung tissues of mice with allergic asthma. Compared with the HDM-induced group, Spon2 knockdown led to decreased levels of inflammatory cytokines in the cellular model and, in the mouse model, it relieved HDM-caused histopathological alterations in mouse lungs, reduced collagen fiber deposition, lowered HDM-specific IgE expression in serum, and mitigated the HDM-induced increase in CD80 expression in lung tissues, total cell counts, and cytokine levels (IL-13, TNF-α, IFN-γ, IL-4, IL-5, IL-10) in BALF. Spon2 plays a role in the progression of HDM-induced allergic asthma and may be a potential therapeutic target worthy of further in vivo investigation.

Recurrent pregnancy loss (RPL), defined as ≥ 2 consecutive losses, remains a significant clinical challenge with complex immunological underpinnings. While immune dysfunction underpins RPL, dendritic cells (DCs) emerge as central regulators of maternal-fetal tolerance. This review comprehensively explores the multifaceted roles of DC subsets at the maternal-fetal interface, including their contribution to immune tolerance, angiogenesis, placental development, and bidirectional interactions with trophoblasts and natural killer (NK) cells. We detail specific DC alterations in RPL, encompassing phenotypic shifts, functional defects, and disrupted DC-NK cell crosstalk, linking these changes to pregnancy loss risk. Emerging evidence highlights therapeutic strategies targeting DCs, such as tolerogenic DC vaccines and interventions modulating trophoblast MHC antigen presentation, alongside established immunomodulation, to restore immune balance. Underlying mechanisms like systemic inflammation impacting endometrial DCs are also discussed. By synthesizing current literature and controversies, this review elucidates the critical, yet complex, role of DC heterogeneity and function in RPL pathogenesis and discusses innovative interventions aimed at improving pregnancy outcomes.