Iranian Journal of Immunology最新文献

Background: Proper invasion and migration of trophoblasts are critical for successful human pregnancy. Tumor necrosis factor-α (TNF-α) has two biologically active forms: the membrane-bound TNF-α (mTNF) and the soluble TNF-α (sTNF).

Objective: To investigate the role of both forms of TNF-α in trophoblasts invasion and migration and to elucidate their underlying mechanisms.

Methods: We exposed HTR-8/SVneo trophoblasts to exogenous mTNF or sTNF and evaluated their cellular behaviors. Proliferation was assessed using a Cell Counting Kit-8, while invasion and migration were assessed through Transwell assays. Additionally, we measured mRNA levels of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1), and plasminogen activator inhibitor-1 (PAI-1) using qRT-PCR. The expression of IκB-α was determined by western blot analysis.

Results: Unlike sTNF, mTNF enhances the invasion and migration of trophoblasts. Mechanistic analysis showed that mTNF increased MMP-9 expression while decreasing TIMP-1 and PAI-1 expression, and it inhibited the activation of NF-κB signaling pathway in HTR-8/SVneo cells with or without lipopolysaccharide (LPS) treatment.

Conclusion: This research uncovered a new function of mTNF in regulating trophoblast invasion and migration, offering a new approach to treating pregnancy-related diseases associated with inadequate trophoblast invasion.

Background: Tumor-draining lymph nodes play a pivotal role in orchestrating immune cell trafficking and initiating antitumor responses. Among immunoregulatory molecules, programmed cell death protein 1 (PD-1) has emerged as a central mediator in tumor-induced immunosuppression.

Objective: To investigate the expression patterns of PD-1 and its ligands (PD-L1, PD-L2) in the tumor-draining lymph nodes of patients with breast cancer (BC).

Methods: Lymph node samples were freshly collected from BC patients undergoing surgery. Mononuclear cells were isolated and analyzed by flow cytometry for surface markers CD45, PD-1, PD-L1, and PD-L2. Data were analyzed using FlowJo v10.8.1.

Results: PD-1 was detected on 9.48 ± 5.19% of CD45+ cells, whereas PD-L1 and PD-L2 were expressed at lower levels (1.73 ± 0.85% and 1.68 ± 0.84%, respectively). Despite a significant reduction in the percentage of CD45+ lymphocytes, the frequencies of PD-1+ and PD-L2+ subsets were significantly elevated in patients with poorly-differentiated and advanced-stage tumors (P<0.05). Additionally, the frequency of PD-1+ lymphocytes was significantly higher in patients with the triple-negative tumors (P=0.014) and in those negative for estrogen and progesterone receptor (P=0.001).

Conclusion: Elevated expression of PD-1 and its ligands in BC-draining lymph nodes is associated with adverse clinical features, suggesting their role in immune evasion. These findings along with higher frequency of PD-1+ lymphocyte in triple-negative patients may inform subtype-specific therapeutic strategies and predict responsiveness to PD-1/PD-Ls blockade therapies. Future studies should include functional analyses with broader immunophenotyping to further elucidate these mechanisms.

Pertussis is a highly contagious respiratory disease caused by the gram-negative bacterium Bordetella pertussis (Bp). The disease is most severe in infants and young children, whereas adolescents and adults typically experience milder symptoms but serve as important reservoirs for transmission. Despite widespread vaccination efforts, pertussis continues to pose a significant public health challenge. Historically, the first generation of pertussis vaccines, formulated as inactivated whole cell pertussis (wP) vaccines, were associated with notable side effects, prompting the development of safer acellular pertussis (aP) vaccines. The second generation of pertussis vaccines contains purified components of Bp and provides protection comparable to that of the older whole-cell vaccines. However, recent studies have reported a resurgence of pertussis, attributed to several factors, including improved diagnostic methods, waning immunity following vaccinations, and the emergence of antigenically divergent or vaccine-adapted strains. To address these challenges, researchers are developing next-generation pertussis vaccines using various approaches, such as transitioning from intramuscular to intranasal administration, formulating outer membrane vesicle (OMV)-based vaccines, designing live attenuated pertussis vaccines, and exploring nucleic acid-based vaccines and novel adjuvants aimed at inducing long-lasting mucosal and systemic immunity. This review primarily focuses on assessing the efficacy of the next-generation intranasally administered pertussis vaccines in both pre-clinical and clinical settings.

Wound healing is a complex and dynamic process that encompasses four interrelated phases: hemostasis, inflammation, proliferation, and remodeling. Inflammation plays a pivotal role in both acute and chronic wound healing. In chronic diabetic wounds, the normal healing rate is impaired due to persistent inflammation, which is associated with unbalanced immune responses. Microbial biofilms, increased immune cell activity, the accumulation of pro-inflammatory cytokines, and free radicals can contribute to the establishment of chronic inflammation in these wounds. Modulating the immune microenvironment in chronic wounds can significantly enhance the process of wound healing and tissue regeneration. Programmed death-ligand 1 (PD-L1) is an important immune checkpoint molecule that can bind to the PD-1 receptor on the immune cells and suppress the immunogenic responses. Although inflammation plays a significant role in wound healing, the role of PD-L1 in chronic wounds is not clearly understood. Interestingly, recent evidence indicates that fibroblast cells in granulation tissues express PD-L1. This paper will review the current findings and potential advantages of PD-L1 in the wound healing process, presenting a novel approach for treating chronic wounds.

Keloid, as a skin fibrotic proliferative disorder, have a complex pathogenesis that remains incompletely understood. It is characterized by abnormal and excessive scar formation following skin injury. The occurrence and development of keloids are closely associated with immune dysregulation. Immune cells, such as T cells, macrophages, mast cells, and Langerhans cells, play crucial roles in the formation of keloids. These immune cells contribute to keloid initiation and progression through mechanisms including cytokine secretion, promotion of inflammatory responses, and regulation of fibroblast proliferation and collagen synthesis. With advances in immunological research, the roles of fibroblasts, keratinocytes and melanocytes in the immunological dysregulation underlying keloids have received increasing attention. This paper aims to review recent progress on the abnormal immunological regulation involving these three epidermal cell types, in order to provide new insights and theoretical foundations for the treatment of this disease.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and progressive destruction of joint structures. Anti-cyclic citrullinated peptide (anti-CCP) antibodies have emerged as highly specific biomarkers, whereas rheumatoid factor (RF) demonstrates lower diagnostic specificity.

Objective: To assess the diagnostic utility of anti-CCP in comparison with rheumatoid factor (RF) in Libyan patients with RA and to investigate their associations with immunological markers, demographic characteristics, comorbid conditions, and clinical manifestations.

Methods: A cross-sectional case-control study was conducted involving 70 RA patients who met the 2010 ACR/EULAR classification criteria and 70 age- and sex-matched healthy controls. Serum concentrations of anti-CCP antibodies, RF, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and complete blood count parameters were measured. Statistical analyses were performed to evaluate associations between serological markers and clinical variables, including sex, age, family history, disease activity, comorbidities, smoking status, COVID-19 vaccination, and vitamin D levels.

Results: Anti-CCP demonstrated a higher positivity rate (78.6%) compared with RF (64.3%) and was negative in all controls, whereas RF yielded false-positive results. Anti-CCP positivity was significantly associated with female sex (p = 0.026), tender joint count, CRP, ESR, neutrophil-to-lymphocyte ratio, platelet count, and mean corpuscular volume. Additional associations were identified with COVID-19 vaccination, smoking, type 1 diabetes mellitus, family history of RA, higher disease activity, and lower vitamin D levels.

Conclusion: Anti-CCP demonstrated superior diagnostic specificity and broader clinical relevance compared with RF. Its strong associations with female sex, family history of RA, comorbidities, and disease activity support the incorporation of anti-CCP testing into routine diagnostic and monitoring protocols for RA in Libya.

Background: Common variable immunodeficiency (CVID) is an inborn error of immunity characterized by a defect in terminal B cell differentiation, resulting in hypogammaglobulinemia and impaired production of specific antibodies. Stimulation via Toll-like receptors (TLRs) has been shown to promote the differentiation and functional maturation of late-stage B cells.

Objective: To assess aberrations in TLR2 signaling among patients with CVID and to explore their associations with clinical manifestations and immunological parameters.

Methods: Sixteen CVID patients and 16 healthy controls were recruited for this individual-matched case-control study. Genetic variants in patients had been previously identified through whole-exome sequencing. TLR2 and TLR4 downstream gene expression were analyzed using qRT-PCR, while cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA). Statistical associations between clinical features and laboratory parameters were analyzed using SPSS software.

Results: Downstream gene expression following TLR2 stimulation was significantly reduced in 25% of CVID patients, while the TLR4 signaling pathway remained largely unaffected. Patients exhibiting TLR2 overexpression demonstrated a later disease onset, presenting with autoimmunity, lymphoproliferation, and atopic manifestations. A consistent immunologic feature among patients with defective TLR2 signaling was the reduction in marginal zone and switched memory B cell populations. Furthermore, Levels of IL-6 and IL-1β following agonist stimulation were significantly lower in CVID patients compared to healthy controls.

Conclusion: This study demonstrates that functional impairment of TLR2 signaling influences the clinical presentation, immunologic profile, and cytokine production in patients with CVID. These findings suggest a potential underlying etiology in a subset of patients with unidentified monogenic defects.

Background: Coronavirus Disease 2019 (COVID-19) typically manifests with milder symptoms and lower mortality rates in children when compared to adults.

Objective: To investigate potential mechanisms underlying this age-related protection, we examined whether serum levels of angiotensin-converting enzyme 2 (ACE2) and IgG antibody titers against Measles, Mumps, and Rubella (MMR) vaccines are associated with susceptibility to SARS-CoV-2 infection in the pediatric population.

Methods: In this case-control study, conducted before the introduction of mass COVID-19 vaccination, we enrolled children aged 1-15 years. The cases were hospitalized children with confirmed COVID-19, while the control group consisted of outpatients with non-infectious, non-immunodeficient conditions and no documented history of COVID-19. The COVID-19 status was confirmed using RT-PCR. Serum levels of ACE2 and anti-MMR IgG antibodies were assessed using ELISA.

Results: Eighty-three patients including 39 cases with COVID-19 infection and 44 controls were enrolled in this study. The median serum ACE2 levels were 3.6 in COVID-19 cases and 3.8 ng/mL in control cases (P=0.440). Similarly, antibody levels against Mumps (P=0.788), Measles (P=0.281), and Rubella (P=0.083) did not differ significantly between the groups, although Rubella seropositivity was more frequent in COVID-19 cases than in controls (P=0.039).

Conclusion: Our findings did not support a significant association between serum ACE2 levels or MMR antibody titers and protection against COVID-19 in children. The higher prevalence of Rubella seropositivity among infected cases may suggest possible cross-reactivity, but causal relationships could not be established in this study.

Background: Antitumor-targeting drugs can stimulate dendritic cells (DCs) indirectly through the shedding of dying tumor cells as part of what is referred to as a "danger signal". Although chemotherapeutic agents have been shown to kill dendritic cells (DCs), the effects of low, non-cytotoxic doses on DC function have not been studied.

Objective: To investigate the impact of various concentrations of mitomycin C at low, non-cytotoxic doses on the maturation of DCs.

Methods: THP-1 monocytes were differentiated into immature dendritic cells using IL-4 and GM-CSF. HCT116 colorectal cancer cells were treated with mitomycin C at concentrations ranging from 10 to 80 nM and co-cultured with undifferentiated dendritic cells. The expression of co-stimulatory molecules (CD11c, CD80, CD83, CD86, HLA-DR, CD14) and IL-12p70 secretion were measured.

Results: Different dosages of Mitomycin C-treated HCT116 cells enhanced the maturation of dendritic cell markers (CD80, CD83, CD86, HLA-DR), but reduced CD14 levels (p< 0.01). While increasing the Mitomycin C dose to 80 nM further upregulated HLA-DR and CD86 expression, the release of IL-12 was highest a 50 nM concentration of mitomycin C (686.7 ± 125.7 pg/mL compared to 263.8 ± 4.8 pg/mL in controls; p < 0.05). IL-12 levels were not significantly increased even with 30 nM Mitomycin C.

Conclusion: Low concentrations of Mitomycin C contributed to an increase in dendritic cellmaturation and an increase in the expression of co-stimulatory molecules (CD80, CD86, CD83, and HLA-DR), along with the secretion of cytokines such as IL-12p70, IL-2, and GM-CSF.