Iranian Journal of Immunology最新文献

Background: Tumor-infiltrating lymphocytes (TILs) and brain stromal cells produce immunosuppressive cytokines, contributing to an immunosuppressive tumor microenvironment (TME). Interleukin-38 (IL-38) is a novel anti-inflammatory cytokine and a natural modulator of the innate and adaptive immune system. However, its biological roles in brain tumors are not well defined.

Objective: To assess the serum levels of IL-38 and the percentages of TILs in the tumor tissues of patients with primary brain tumors and to determine their associations with the pathological features of the disease.

Methods: IL-38 was evaluated in sera using the enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (H&E)-stained sections were scored to determine the percentages of TILs in four different areas: the invasive margin, central tumor, perivascular and perinecrotic areas.

Results: IL-38 serum levels were significantly higher in low- and high-grade tumors than in healthy individuals, meanwhile, its levels remained consistent between these two grades. Although no significant difference was found in IL-38 serum levels between different histological subtypes of brain tumors, its levels were significantly higher in intra-axial brain tumors than in extra-axial ones. Additionally, a significant positive correlation was observed between serum levels of IL-38 and tumor size in patients with low-grade tumors. TILs were detected in at least one of the four examined areas; however, no statistically significant correlation was found between IL-38 levels and TILs.

Conclusion: Our data may suggest a connection between IL-38 and immune suppression and tumor progression in primary brain tumors. Further investigation is needed to uncover the role of IL-38 in the brain tumor microenvironment.

Background: Endometriosis is a medical condition that can cause infertility in women. Women with endometriosis experience a decrease in NK cell cytotoxic activity against endometrial cells, ultimately contributing to the spread of these cells.

Objective: To assess the frequency of NK cells and the expression of the NKP46 receptor in endometrial tissue from patients with endometriosis using immunohistochemistry.

Methods: 30 endometrial tissue specimens were collected from three groups of cases with mild (n=11), moderate (n=10), and severe endometriosis (n=9), respectively. Additionally, 20 normal endometrial tissue specimens were collected as the control group. Immunohistochemical staining was carried out using specific human monoclonal antibodies against CD56 and NKP46 molecules.

Results: Cases with severe endometriosis had a significantly higher number of CD56+ uterine NK cells (26.19±2.50) compared to fertile women (15.02±0.622) and women with mild to moderate endometriosis (p<0.001). However, there was no significant difference between the mild to moderate patients compared with the healthy women (p>0.05). Endometrial NKp46 expression was lower in women with severe endometriosis (0.447±0.0829) compared to fertile women (0.987±0.115, p=0.03). The NKp46+/CD56+ cell ratio was also lower in women with severe endometriosis (0.019±0.003) compared to fertile women (0.072±0.011, p=0.01).

Conclusion: Women with severe endometriosis demonstrated an increased rate of infiltrated uterine NK cells and a significant decrease in NKP46 expression compared to fertile women. Therefore, NK cells and the NKp46 receptor may be involved in the development of endometriosis.

Background: Pulmonary neutrophils may play a crucial role in the development of bronchiolitis obliterans (BO) following measles virus infection. IL-27 could potentially have a negative regulatory effect on the release of reactive oxygen species and cytotoxic granules in neutrophils.

Objective: To investigate the levels of IL-27 in the bronchoalveolar lavage fluid (BALF) of children with post-infectious bronchiolitis obliterans (PIBO) and analyze the relationship between IL-27 levels and neutrophil proportions.

Methods: A total of 24 children with PIBO were recruited for the experimental group, while 23 children with bronchial foreign bodies were included in the control group. Bronchoscopic alveolar lavage was performed in both groups. The levels of IL-27 in BALF were measured using enzyme-linked immunosorbent assay (ELISA). The proportions of neutrophils in BALF were determined by smear staining. The relationship between the levels of IL-27 in BALF and the neutrophil proportions was analyzed by the Pearson test.

Results: The levels of IL-27 in BALF were significantly lower in children with PIBO compared to children with bronchial foreign bodies (p<0.05). Additionally, the proportions of neutrophils in BALF were significantly higher in children with PIBO compared to children with bronchial foreign bodies (p<0.05). The levels of IL-27 were negatively correlated with the neutrophil proportions in BALF in children with PIBO (p<0.05), but not in children with bronchial foreign bodies (p>0.05).

Conclusion: The present study suggests that a decrease in IL-27 may be associated with an increase in neutrophils in BALF and may contribute to the pathogenesis of PIBO.

Background: Natural killer (NK) cells play a role in the pathogenesis of various metabolic diseases related to obesity. While our initial findings have indicated a potential involvement of NK cells in the pathogenesis of type 2 diabetes mellitus, the precise mechanism underlying NK cell-mediated development of this form of diabetes remains inadequately comprehended.

Objective: To investigate the impact and the underlying mechanism of high glucose and elevated levels of free fatty acids (FFAs) on immune and inflammatory responses and oxidative stress in NK92 cells.

Methods: In this experiment, the CCK8 cytotoxicity assay was used to select the 44.4 mM and 1.5 mM concentrations of high glucose and high FFAs, respectively, to treat NK92 cells for 4 days. The concentrations of superoxide dismutase (SOD) and glutathione (GSH) were determined using a biochemical analyzer. Intracellular reactive oxygen species (ROS) levels, cytokines concentrations (TNF-α, IFN-γ, IL-6, and IL-10), and the expression levels of intracellular molecules (perforin and granzyme B) were assessed by flow cytometry.

Results: The number of NK92 cell clumps was significantly reduced in the high-FFA (HF) group. In addition, the production of ROS and levels of cytokines (TNF-α, IFN-γ, IL-6, and IL-10) significantly decreased in the HF group but showed no significant change in the high-glucose (HG) group. This observation was consistent with the expression levels of perforin and granzyme B that decreased in the HF group.

Conclusion: High FFAs induced morphological changes and serious damage to oxidative stress and inflammatory response in NK92 cells.

Cell-mediated immunity (CMI) is crucial in controlling the highly aggressive and progressive SARS-CoV-2 infection. Despite extensive researches on severe COVID-19 infection, the etiology and/or mechanisms of lymphopenia, decreased T cell-mediated responses in patients, cytokine release storms (CRS), and enhanced pro-inflammatory mediators are not fully understood. Several T cell subpopulations, including innate-like lymphocytes (ILLs) and conventional T cells, are involved in COVID-19 infection; however, their contribution to immunity and complications remains to be more elucidated. CD16+ T cells are among the effective players in the development of T helper1 (Th1) responses in COVID-19 infection, while their robust cytolytic properties contribute to lung tissue damage. While CD56-CD16bright NK cells play a protective role, natural killer T (NKT) cells, mucosal-associated invariant T (MAIT) cells, and γδ T cells and their roles in COVID-19 require further investigation. The involvement of the other T cell subsets, such as Th17, along with neutrophils, adds to the complexity of the situation. In this review, we presented and discussed the findings of recent studies on T cell responses and the contribution of each type of immune cells to COVID-19.

Hemophagocytic lymphohistiocytosis (HLH) is a fatal clinical syndrome. The most common cause of secondary HLH is Epstein-Barr virus (EBV) infection. EBV-HLH is a common clinical disease with high mortality, easy relapse, and poor prognosis. Therefore, treating EBV-HLH with T and B lymphocyte involvement is challenging, and selecting an appropriate treatment regimen is critical. Moreover, research on how to evaluate the recurrence index after remission is scarce. In this study, we reported a case of EBV-HLH successfully treated with programmed cell death protein-1 (PD-1) inhibitor in combination with rituximab. The regimen had a good curative effect, and we successfully detected the trend of early recurrence. Our findings indicated that PD-1 inhibitor in combination with rituximab may help to treat EBV-HLH and maintain EBV-infected T and B whole-line lymphocytes.

Background: Periodontitis is a chronic inflammatory condition that affects the tissues supporting the teeth, ultimately leading to tooth loss. Mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) play a crucial role in periodontitis by modulating the activities of gum cells and the immune system.

Objective: To investigate the therapeutic potential of human umbilical cord mesenchymal stem cells (hUCSCs) and EVs in regulating the inflammatory response associated with periodontitis.

Methods: hUCSCs were isolated, subjected to flow cytometry analysis of surface markers, and differentiated into adipocyte and osteocyte. hUCSC-EVs were isolated and characterized using flow cytometry and electron microscopy. A periodontitis animal model was established in 30 female C57Bl/6 mice. Experimental groups received hUCSCs or hUCSCs-EVs, or vehicles intravenously. Animals were monitored for 4 weeks, and the periodontal tissues were used to assess the effects of hUCSCs and hUCSCs-EVs on the expression of pro- (TNF-α, IFN-γ, and IL-17a) and anti-inflammatory cytokines (TGF-β, IL-10, and IL-4). The secretion of these cytokines by splenocytes was also evaluated using ELISA.

Results: The levels of IL-17a, IFN-γ, and TNFα significantly reduced, while TGF-β and IL-10 significantly increased in the periodontal tissues of the hUCSC and hUCSCEVs-treated mice. The expression of TNF-α, IFN-γ, and IL-17a significantly decreased, while the production of IL-10 and TGF-β significantly increased in splenocytes from the hUCSC and EVs-treated mice.

Conclusion: hUCSCs and their EVs have the potential to attenuate the inflammatory response associated with periodontitis, possibly by downregulating pro-inflammatory cytokines and upregulating anti-inflammatory ones.

Background: Thymocyte selection-associated high mobility group box protein (TOX) and members of the nuclear receptor 4A (NR4A) are known as transcription factors involved in T cell exhaustion.

Objective: To evaluate the mRNA expression of TOX and NR4A1-3 in CD8+ T cells in acute leukemia.

Methods: Blood samples were obtained from 21 ALL and 6 AML patients as well as 20 control subjects. CD8+ T cells were isolated using MACS. Relative gene expression of TOX and NR4A1-3 was then evaluated using qRT-PCR.

Results: Comparison of mRNA expression of TOX in CD8+ T cells showed no significant difference among the study groups (p>0.05), while the expression of NR4A1 was significantly lower in AML patients than in the control group (p=0.0006). Also, the expression of NR4A2 and NR4A3 was significantly lower in both ALL (p=0.0049 and p=0.0005, respectively) and AML (p=0.0019 and p=0.0055, respectively) patients.

Conclusion: NR4As expressions were found to be lower in CD8+ T cells from patients with AML and ALL compared to controls, whereas the mRNA expression of TOX showed no significant difference. Although TOX and NR4As are associated with CD8+ T cell exhaustion in solid tumors, they might play different roles in acute leukemia, which requires further investigation.

Background: T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) is a regulatory molecule expressed on a variety of cell types, including CD3+ T cells. Few studies have been conducted to look into the correlation between TIM3 expression on peripheral T lymphocytes and post-stroke depression (PSD).

Objective: To investigate the relationship between TIM3 expressions on peripheral T lymphocytes in PSD patients.

Methods: Acute stroke patients without depression (NPSD) (n=65), PSD patients (n=23), and body mass index (BMI), age, and education-matched healthy controls (HC) (n=59) were enrolled. Using flow cytometry, TIM3 expression was examined in the peripheral CD3+ CD4+ and CD3+ CD8+ T lymphocytes. Evaluation of the depressive severity in PSD patients was assessed using a 17-item Hamilton Depression Rating Scale (HAM-D-17). We used enzyme-linked immunosorbent assay (ELISA) to determine the serum concentrations of IL-1β, IL-6, IL-10, and IL-18. We further assessed the relationships between TIM3 expression, serum cytokine levels, and the HAM-D-17 scores.

Results: CD3+ CD4+ T cells reduced significantly in PSD patients compared with the NPSD patients and HC. Both NPSD patients and PSD patients had a significant increase in TIM3 expression in their peripheral CD3+ CD4+ T lymphocytes, compared with HC. In PSD patients, a higher frequency of peripheral CD3+ CD8+ T lymphocytes showed significant expression of TIM3 compared to NPSD patients and HC. High TIM3 level on peripheral CD3+ CD8+ T lymphocytes was positively associated with the HAM-D score.

Conclusion: Patients with PSD exhibit immune dysfunction. TIM3 might contribute to the development and severity of PSD, making it a potential therapeutic target.