Journal of Immunology Research最新文献

Background: B7-H4 is an immunosuppressive molecule extensively studied in tumor diseases and is also of interest in some autoimmune diseases. However, the relationship between B7-H4 and autoimmune thyroid diseases (AITDs) has not been explored.

Objective: To investigate the B7-H4 expression in different tissues of patients with different subtypes of AITDs.

Methods: The B7-H4 protein expression in thyroid tissue of the participants was identified through immunohistochemical analyses while concentrations of plasma soluble B7-H4 (sB7-H4) were detected by enzyme-linked immunosorbent assay (ELISA). Additionally, B7-H4 mRNA expression in peripheral blood mononuclear cells (PBMCs) was evaluated via RT-PCR.

Results: The immunohistochemical findings revealed a decrease in levels of B7-H4 protein in thyroid tissue of Graves' disease (GD) and Hashimoto's thyroiditis (HT) patients, compared with those of the normal controls. Similarly, a decrease was observed in the level of B7-H4mRNA expression in PBMCs assayed via RT-PCR. However, based on ELISA results, plasma levels of sB7-H4 were increased in both GD and HT patients compared to those in normal controls.

Conclusion: The abnormal expression of B7-H4 in AITD patients suggests that it may be involved in the onset and progression of the disease. At the same time, the mechanism of action of B7-H4 in AITD and whether it is a potential therapeutic target need to be further studied.

Introduction: Coronavirus disease 2019 (COVID-19) may have both short- and long-term impacts on the progression of human immunodeficiency virus (HIV)-1 after acute SARS-CoV-2 infection in people living with HIV (PLWH), even those on combined antiretroviral therapy (cART). This study aimed to investigate whether SARS-CoV-2 could influence HIV reactivation in latently infected lymphoid cells.

Methods: HIV-infected lymphoid (J-Lat) cells, characterized by proviral latency under unstimulated conditions, were used for latency reversal assays with phorbol 12-myristate 13-acetate (PMA), free SARS-CoV-2 particles, or conditioned media (CM) from macrophages. Monocytes isolated from donor blood were differentiated into macrophages (monocyte-derived macrophages [MDMs]) and polarized to M1 or M2 phenotypes before stimulation or with two SARS-CoV-2 variants (wild-type and BA.5) infection. Additionally, the effects of redox imbalance on latency reversal in both J-Lat and myeloid (U1) latency models were measured. SARS-CoV-2 RNA was quantified by RT-qPCR targeting ORF1ab and N genes, and latency reversal and reactive oxygen species (ROS) levels were assessed by flow cytometry. TNFα involvement was confirmed through neutralization assays, while cytokines and polarization markers were analyzed via ELISA and fluorescent antibodies.

Results: Jurkat and J-Lat cells had low ACE2 expression and were not permissive to SARS-CoV-2 infection. SARS-CoV-2 exposure alone did not induce HIV latency reversal in J-Lat cells. However, CM from M1-polarized, resiquimod (R-848)-treated, and SARS-CoV-2-infected macrophages significantly reactivated latent HIV. TNFα was identified as the primary driver of latency reversal, with no significant changes in ROS levels. Prolonged SARS-CoV-2 exposure shifted macrophage polarization toward an anti-inflammatory M2 phenotype, characterized by IL-10 release, which reduced latency reactivation.

Conclusions: This study demonstrates that SARS-CoV-2 can indirectly reverse HIV latency in lymphoid cells by promoting the release of pro-inflammatory cytokines from infected macrophages. These findings suggest potential therapeutic strategies for preventing HIV reactivation during SARS-CoV-2 coinfection, emphasizing the modulation of cytokine signaling to control inflammation while minimizing immune dysregulation.

Background: Acute graft-versus-host disease (aGvHD) is a major immune complication of allogeneic hematopoietic stem cell transplantation (Allo-HSCT), driven by complex immune-cytokine interactions. This study employed machine learning (ML) algorithms to develop early predictive models for aGvHD using immune and cytokine profiles of Allo-HSCT recipients at the time of engraftment.

Materials and methods: Seventy patients with hematological disorders undergoing their first Allo-HSCT were recruited prospectively. Peripheral blood immune subsets and cytokines were analyzed using flow cytometry and ELISA, respectively. ML models, including support vector classifier (SVC), decision tree, and random forest, were trained on 48 features: 34 immune subsets and 14 cytokines.

Results: Patients who developed aGvHD exhibited a reduced CD4⁺/CD8⁺ ratio, lower Tregs, elevated Th1, Th17, cytotoxic natural killer (NK) cells, dendritic cells (DCs), B cell, and increased proinflammatory cytokines (IFN-γ, IL-1β, IP-10, TNF-α, IL-17α, IL-12p70, MIP-1α, MIP-1β, and RANTES). ML models demonstrated excellent predictive performance, with cytokine profiles alone or combined with immune data achieving perfect accuracy (1.00), followed by T-cell (0.96), NK cell (0.93), DC (0.90), and B cell (0.86) models.

Conclusion: Cytokine profiles emerged as superior predictors over immune subsets, supporting their integration into ML-based aGvHD risk prediction. These findings provide a foundation for developing biomarker-guided strategies for early aGvHD detection and management.

Objective: Primary Sjögren's syndrome (pSS) is a heterogeneous autoimmune disorder with diverse clinical manifestations and limited effective therapies. This study aimed to stratify pSS patients into distinct immunophenotypic subgroups based on peripheral lymphocyte profiles and to explore the clinical relevance of these subgroups, thereby informing personalized management for pSS.

Methods: A retrospective cohort of 133 Chinese pSS patients and 241 age- and sex-matched healthy controls (HCs) was analyzed. Immunophenotyping of 11 lymphocyte subsets was performed using flow cytometry in peripheral blood. K-means clustering was employed to identify patient subgroups based on lymphocyte profile. Clinical data were collected and compared across clusters.

Results: Lymphocyte profiles in pSS patients differed from those in HCs, featuring elevated proportions and estimated counts of activated CD8⁺ T cells along with reduced naïve CD4⁺ T cells and NK cells. Unsupervised clustering analysis identified three distinct patient subgroups based on immunophenotypic patterns: Cluster 1 was characterized by significantly higher proportions of CD8⁺ T cells and showed more frequent hematologic and serological abnormalities, including higher rates of hyperglobulinemia, anti-Ro52 positivity, and high-titer ANA positivity. Cluster 2 was distinguished by higher NK and B cell proportions and clinically presented with greater pulmonary and hepatic involvement along with higher disease damage scores. Cluster 3 maintained lymphocyte distributions closest to HCs but exhibited more frequent constitutional symptoms and cutaneous involvement coupled with lower serological activity.

Conclusion: Lymphocyte profiling may help stratify pSS patients into clinically distinct subgroups, potentially corresponding to different pathobiological endotypes, and could thus inform patient stratification.

Objective: Rheumatoid arthritis (RA) is a common chronic and systemic autoimmune disease. Long noncoding RNAs (lncRNAs) have been documented to play important roles in the pathogenesis of RA. This study is aimed to investigate the differentially expressed lncRNAs in RA and explore the underlying roles and mechanisms of RA-specific lncRNAs.

Methods: Peripheral blood mononuclear cells (PBMCs) from three RA patients and three healthy controls were detected by transcriptome sequencing analysis. Enrichment analysis was performed to identify the potential functional categories and signal pathways. The expressions of the screened dysregulated lncRNAs in RA were further validated using quantitative real-time polymerase chain reaction (qRT-PCR). The effects of the candidate lncRNA lnc-CHRM4-2:1 on the proliferation and apoptosis of Raw264.7 cells were determined by cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) proliferation assays, and Annexin V-APC/PI staining flow cytometry assay. qRT-PCR and western blot were performed to detect the expression of functional molecules related to M1/M2 macrophage polarization and efferocytosis.

Results: The expression of lnc-CHRM4-2:1 was significantly higher in PBMCs of RA patients compared to healthy controls. Lnc-CHRM4-2:1 was negatively associated with the level of serum CCP of RA patients, suggesting that it was a RA-specific lncRNA. Overexpression of lnc-CHRM4-2:1 could potentially affect cell proliferation and apoptosis, promote M1 polarization, inhibit M2 polarization, and the mRNA and protein expressions of MerTK and SLC2A1 in Raw264.7 cells.

Conclusion: Lnc-CHRM4-2:1 is an RA-specific lncRNA, which inhibits macrophage M2 polarization and efferocytosis by downregulating MerTK and SLC2A1. Lnc-CHRM4-2:1 may be considered a potential diagnostic biomarker and therapeutic target for RA.

Interferon-gamma (IFN-γ) is a central mediator of immune-driven bone marrow failure (BMF) in acquired aplastic anemia (AA). Persistent IFN-γ signaling alters the bone marrow microenvironment by activating the JAK-STAT1 pathway, which results in immunological imbalance, inflammatory amplification, and depletion of hematopoietic stem and progenitor cells (HSPCs). IFN-γ disturbs HSPC quiescence and self-renewal, interferes with thrombopoietin (TPO)-c-Mpl communication, and stimulates cytotoxic T-cell-dominant immunological responses. Simultaneously, IFN-γ destabilizes local immunological homeostasis by disrupting immune crosstalk through the IDO1 axis and regulatory T-cell (Treg) malfunction. In addition to discussing new therapeutic methods, such as Treg-based therapies and JAK inhibition, as prospective precision approaches for AA, this review incorporates current mechanistic insights into IFN-γ-driven cellular interactions inside the bone marrow niche.

The specific immune response mechanisms of B cells and T cells are centered on the classic clonal selection theory, which posits that "a single lymphocyte expresses only one type of antigen receptor." This mechanism is primarily achieved through V(D)J allelic exclusion rearrangement on germline chromosomes and rigorous self-tolerance selection. However, accumulating experimental evidence indicates that phenomena such as incomplete allelic exclusion rearrangement (i.e., allelic inclusion rearrangement), escape from central tolerance selection, and peripheral immune receptor editing can induce the generation of dual-receptor lymphocytes, including "dual-BCR B cells," "dual-TCR T cells," and "TCR⁺BCR⁺ lymphocytes." This article systematically reviews the research overview and recent advances in dual-receptor lymphocytes in humans and mice under physiological and pathological conditions. By integrating theoretical model construction and validation results from immune molecular monitoring techniques, it emphasizes the proportional characteristics, biological effects, and possible origins of dual-receptor lymphocytes. It also explores their association with disease development, aiming to provide a theoretical foundation and novel research perspectives for in-depth studies in this field.

Objective: To systematically characterize the peripheral immune signature of uterine fibroids (UFs) and to develop a diagnostic model for differentiating UF patients from healthy individuals, thereby providing new insights into UF immunopathogenesis.

Methods: We performed multiparametric flow cytometry analysis on peripheral blood samples from 31 UF patients and 63 age-matched healthy controls (HCs). A total of 70 immune parameters were evaluated, encompassing T cells, B cells, natural killer (NK) cells, γδ T cells, and their functional subsets.

Results: Comprehensive immunophenotyping revealed a distinct peripheral immune profile in UF patients. Key findings included a significant dysregulation within helper T (Th) cell compartments, characterized by elevated frequencies of functional Th and Th17 cells, alongside reduced proportions of senescent Th, T follicular helper 1 (Tfh1), and peripheral Th (Tph) cells. Concurrently, a significant expansion of the B cell compartment was observed, marked by increased total B cells, naïve B cells, immature regulatory B cells (Breg), and transformed B cells. In contrast, the frequencies and functional subsets of cytotoxic T (Tc) cells, γδ T cells, and NK cells showed no significant alterations after false discovery rate (FDR) correction. A random forest (RF) model incorporating key immune markers effectively discriminated UF patients from HCs, identifying several markers as central features with both diagnostic and mechanistic relevance.

Conclusion: This study presents the first systematic atlas of the peripheral immune landscape in UF, revealing a pattern of systemic immune dysregulation centered on Th and B cell pathways. These findings advance our understanding of the immunopathogenesis of UF and establish a foundation for future immune-based diagnostic and therapeutic strategies.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that have been increasingly defined and characterized over the past two decades, known for their remarkable capacity to expand and exert immunosuppressive effects in various pathological contexts, such as malignancies, infections, and inflammatory diseases. Although MDSCs have attracted significant attention in tumor immunology, their multifaceted roles in immune-mediated hematological disorders remain comparatively understudied and less understood, especially in contrast to their well-documented functions in both solid and hematological malignancies. This review delves into the biological characteristics and functional mechanisms of MDSCs, as well as their dual immunomodulatory roles in various immune-mediated hematological disorders such as immune thrombocytopenia and aplastic anemia. Substantial evidence indicates that in these diseases, the expansion, recruitment, and function of MDSCs are significantly altered, with their levels closely correlated to disease activity. Based on these findings, we further explore the therapeutic potential of targeting MDSCs. Manipulating MDSCs offers a pioneering perspective for the development of next-generation immunotherapies, which holds promise for reshaping the current treatment landscape of immune-mediated hematological disorders.