Journal of Immunology Research最新文献

[This corrects the article DOI: 10.1155/2018/6529681.].

Chronic stress is an established etiological factor for numerous pathologies, including cancer, yet the underlying molecular etiology remains incompletely understood. This review elucidates a critical molecular axis through which chronic stress promotes carcinogenesis via the bidirectional interaction between the glucocorticoid receptor (GR) and nuclear factor-κB (NF-κB). The review comprehensively details how chronic stress induces pathological GR signaling, characterized by post-translational modifications (PTMs), glucocorticoid (GC) resistance, and altered expression of receptor isoforms. This impairment of GR function leads to the disinhibition of proinflammatory transcription factor, NF-κB. This disinhibition results in sustained NF-κB hyperactivation, which orchestrates a protumorigenic microenvironment by driving genetic instability, immune evasion, uncontrolled proliferation, apoptosis resistance, angiogenesis, and metastasis. By providing an integrative synthesis of these interconnected pathways, this review offers a novel mechanistic framework that directly links the molecular consequences of chronic stress to the hallmarks of cancer. This work therefore establishes the GR/NF-κB signaling interface as a critical and therapeutically targetable mediator of stress-induced carcinogenesis.

Neutrophils have been generally considered to be homogeneous cells with only antimicrobial functions. Nowadays, however, it is clear that neutrophils are heterogeneous cells, with multiple phenotypes and functional states. One neutrophil subpopulation, the low-density neutrophils (LDN) are found among peripheral blood mononuclear cells (PBMC) after separating blood cells by density gradient centrifugation. LDN have attracted a lot of interest because they increase dramatically in several pathological conditions. LDN have been mostly studied in systemic lupus erythematosus (SLE). In this disease, LDN are prone to produce neutrophil extracellular traps (NETs) and to secrete larger amounts of proinflammatory cytokines. However, in the context of cancer, LDN are described as immunosuppressive cells and have been called granulocytic-myeloid-derived suppressor cells (G-MDSCs). Moreover, in the case of many other diseases, there is very little information on the functional properties of LDN. Hence, LDN not simply increase in numbers but become functionally different during distinct disease states. This has created confusion in the field, and the characteristics and functions of LDN continue to be a contentious issue. In this review, we aim to bring together current research in the field of LDN. We discuss discrepancies in the literature in relation to the identification and functional characterization of LDN, and also the possibility that LDN could become a biomarker for some inflammatory conditions and even novel therapeutics for certain diseases.

Background: The bone marrow (BM) microenvironment plays a crucial role in acute myeloid leukemia (AML), but the distribution and clinical significance of monocyte subsets within this compartment remain poorly characterized. This study aimed to investigate the composition of BM monocyte subpopulations and their relationship with systemic immunity and clinical outcomes in AML patients.

Methods: We collected BM samples from 98 AML patients (including 23 newly diagnosed, 28 nonremission, and 47 complete remission [CR] cases) and 23 healthy controls (HCs). Using flow cytometry, we analyzed monocyte subsets (classical, intermediate, nonclassical) and monocytic myeloid-derived suppressor cells (m-MDSCs) in BM, along with T lymphocyte subsets in peripheral blood. Survival analysis was performed with 1-year follow-up data.

Results: Both the proportion of intermediate monocytes and m-MDSCs among total monocytes were significantly elevated in newly diagnosed AML patients compared to those in HCs (p  = 0.019 and p  = 0.003, respectively) and CR (p = 0.003 and p = 0.037, respectively). This elevation was followed by a gradual decrease from diagnosis to remission. Multivariate Cox regression identified intermediate monocyte percentage as an independent prognostic factor (HR = 4.170, p = 0.034). Kaplan-Meier analysis confirmed that higher intermediate monocyte levels predicted shorter overall survival (OS) (p = 0.031) and leukemia-free survival (LFS) (p = 0.028). Importantly, negative correlations were observed between BM blasts and peripheral blood T-cell percentage (r = -0.467, p = 0.005) and CD8⁺ T cells (r = -0.504, p = 0.002), and between intermediate monocytes among total monocytes and total T-cell percentage (r = -0.475, p = 0.004).

Conclusions: BM monocyte subsets, particularly intermediate monocytes, serve as significant indicators of disease progression and survival in AML. Their correlation with peripheral T-cell immunity suggests their potential role in modulating antileukemic immune responses. These findings highlight the prognostic value of BM monocyte profiling and provide insights for developing novel immunotherapeutic strategies in AML.

In addition to its classical function in regulating phosphorus and calcium equilibrium, the immunoregulatory effects of vitamin D (VD) have increasingly drawn attention in recent investigations. A deficiency of VD has been associated with multiple autoimmune pathologies. Immune thrombocytopenia (ITP), a hemorrhagic disorder mediated by autoantibodies, manifests through accelerated platelet destruction accompanied by impaired platelet production. Accumulating evidence suggests that VD is intricately involved in ITP pathophysiology, with serum VD concentrations strongly associated with clinical symptoms, disease severity, and overall prognosis. However, the mechanisms underlying these associations remain incompletely understood, and the limited number of studies conducted thus far highlights the necessity for further investigation. This study reviews the correlation between VD and ITP, the immunological mechanisms through which VD regulates ITP, and the potential therapeutic value of VD supplementation in ITP management. Future multicenter clinical trials and mechanistic studies are warranted to develop novel therapeutic strategies for ITP.

Introduction: Infection with HIV alters γδ T cells, and while these changes have been well documented in blood, they are less well understood in the gut.

Methods: Phenotype (specifically HIV coreceptor expression) and polyfunctionality, as defined by concomitant cytokine expression, were evaluated in γδ T cells in the blood and gut of effectively treated people living with HIV (PLWH) and people without HIV (PWOH). Mononuclear cells were isolated from blood and recto-sigmoid colon biopsy tissue, and γδ T cells were evaluated by flow cytometry.

Results: The expression of α4β7 was significantly higher in gut-derived γδ T cells of PLWH compared to PWOH and blood-derived cells of both groups. The polyfunctionality profile of gut-derived γδ T cells in PLWH was also different than that of PWOH, with significantly higher expression of IFN-γ in the gut-derived cells.

Conclusion: The alterations observed in gut-derived γδ T cells from effectively treated PLWH suggest cellular function is not restored with prolonged antiretroviral therapy (ART) and may contribute to a chronic inflammatory state. Trial Registration: HAVARTI trial registration (ClinicalTrials.gov): NCT03147859.

[This corrects the article DOI: 10.1155/2021/6688053.].

Background: Idiopathic granulomatous mastitis (IGM) is a chronic inflammatory breast disorder with unclear etiology. Isthmin-1 (ISM1), a secreted protein with anti-inflammatory properties, has not been previously studied in IGM.

Objective: This study aimed to compare serum and tissue ISM1 levels between IGM patients and healthy controls, and to assess its diagnostic potential.

Methods: This case-control study included 30 women with histopathologically confirmed IGM and 30 age-matched controls undergoing breast reduction surgery. Serum and tissue ISM1 levels were measured using ELISA. Receiver operating characteristic (ROC) analysis assessed the diagnostic performance of serum ISM1.

Results: ISM1 concentrations were significantly lower in IGM patients compared to controls in both serum (541.42 ± 191.01 vs. 1139.19 ± 698.43 pg/mL; p = 0.019) and tissue (511.07 ± 188.16 vs. 778.24 ± 261.98 pg/mL; p  < 0.001). ROC analysis demonstrated moderate diagnostic accuracy (area under the curve [AUC]: 0.768, 95% CI: 0.651-0.885; optimal cutoff: 676.13 pg/mL; sensitivity: 66.7%; specificity: 83.7%). Standard inflammatory markers showed no significant differences between groups.

Conclusions: Reduced ISM1 levels in IGM patients suggest potential involvement in disease pathogenesis. While serum ISM1 shows promise as a supportive biomarker, larger studies, including other inflammatory breast conditions, are needed to confirm specificity and clinical utility.

[This retracts the article DOI: 10.1155/2022/1178874.].

There is compelling evidence that complement plays a major role in the elimination of nonparasitized erythrocytes (np-Es) in the anemia of malaria. In fact, for every erythrocyte destroyed after infection by Plasmodium falciparum (Pf) or Plasmodium vivax, at least 10 np-Es are cleared, most likely due to C3b opsonization. In malaria, complement is activated by three breakdown products released from lysed parasitized erythrocytes (p-Es): hemin/hematin, the digestive vacuole (DV), and hemozoin. Both childhood anemia in malaria and post-artesunate delayed-hemolysis in individuals with malaria treated with artesunate can be ascribed to complement activation. These findings are important with respect to development of potential therapies for malarial anemia because there are now available FDA-approved drugs that completely inhibit complement at the C3 activation step for several days at a time. We review key clinical findings and basic science investigations that implicate complement and in particular C3b opsonization as a significant factor in malarial anemia. Extension of these basic science studies to examine FDA-approved drugs that block complement at the C3b opsonization step are needed to justify their potential utilization in treatment of malarial anemia. In particular, in vitro studies in blood cultures of Pf/vivax should determine whether deposition of C3 activation products on np-Es can be completely prevented in the presence of complement inhibitors. If these experiments validate proof of concept, then extension of this paradigm to a clinical trial based on combined treatment with artesunate plus an FDA-approved complement inhibitor would be indicated.