Journal of Immunology Research最新文献

Spontaneous preterm labor (SPTL) is a major cause of neonatal mortality and severe complications. T cells play a crucial role in mediating inflammation and immune tolerance at the maternal-fetal interface. T helper 17 cells (Th17, pro-inflammatory) and regulatory T cells (Treg, anti-inflammatory) are two subsets of CD4⁺ T cells with opposite functions, and their balance is important for maintaining immune homeostasis. Since infection and inflammation represent prominent factors responsible for the pathogenesis of SPTL, Th17/Treg imbalance at the maternal-fetal interface may trigger proinflammatory responses, potentially leading to SPTL. In this review, evidence from both clinical cases of SPTL and animal models indicates the presence of Th17/Treg imbalance in both peripheral blood and the maternal-fetal interface. Additionally, interleukin-6 (IL-6), interleukin-1β (IL-1β), and interleukin-8 (IL-8) have been involved in the pathogenesis of inflammation-induced SPTL, suggesting that Th17/Treg imbalance may have relevance to and be involved in the pathogenic process of SPTL. Moreover, the presence of Th17/Treg imbalance in risk factors for SPTL, such as autoimmune diseases and bacterial infections, further supports this connection indirectly. Although predictive models and interventional strategies related to SPTL have been explored, there is currently insufficient evidence to establish a direct causal relationship between Th17/Treg imbalance and the onset of SPTL.

Problem: Antiretroviral therapy (ART) during pregnancy is essential to prevent vertical HIV transmission and preserve the health of the mother and child. However, ART in pregnancy has been associated with adverse birth outcomes linked to poor placental development. Immune dysregulation of placental development is an important factor in the development of preeclampsia (PE), a common hypertension disorder of pregnancy. Some studies found an association between ART use at conception or during the first trimester and PE. However, little is known regarding the impact of timing of ART initiation on the immune environment in pregnancy. Methods: To investigate the immune environment in pregnant persons with HIV (PPWH) on ART at conception (N = 40) compared to PPWH that started ART in the second trimester (N = 40) we analyzed specimens from the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Perinatal Core Protocol, P1025, concluded in 2013. Results: No difference was found in soluble factors in circulation including PlGF and sFLt-1, associated with PE. However, upon analysis of PBMC by high dimension flow cytometry, we detected a lower frequency of circulating CD49a⁺ NK cells, associated with uterine tissue and pregnancy, in PPWH on ART at conception compared with PPWH who started ART in the second trimester. Moreover, PBMC from PPWH on ART at conception expressed higher levels of SERPINB2 in transcriptomics analyses. Conclusions: Our findings shed new insights into the potential impact of ART at conception and suggest the persistence of a dysregulated inflammatory environment compared to PPWH starting ART after the conclusion of placental development.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection spans a spectrum of symptoms, ranging from mild respiratory issues to severe outcomes like pneumonia, acute respiratory distress syndrome, and fatality. Natural killer (NK) cells, governed by killer cell immunoglobulin-like receptors (KIRs), play a pivotal role in directly combating viral infections. Emerging studies indicate a decline in NK cell numbers and heightened NKG2A expression in infected individuals. Objective: This study focuses on genotyping human leukocyte antigen (HLA)-E, HLA-G, and KIR in SARS-CoV-2-positive individuals, comparing data between those with mild and moderate/severe symptoms. The cohort comprised 100 COVID-19-positive patients and 100 healthy volunteers, both groups subjected to DNA isolation and genotyping using sequence-based sequencing. Results: In 97 COVID-19-positive patients (52 mild, 24 moderate, and 21 severe) and 100 healthy volunteers, the study revealed protective associations with inhibitory alleles (KIR2DL1, KIR2DL3, KIR2DL4, KIR3DL1, KIR3DL2, and pseudo-alleles like KIR3DP1⁣ ^∗ 003). Conversely, predisposing factors included activator alleles (KIR2DS2, KIR3DS1) and pseudo-alleles (KIR3DP⁣ ^∗ 001/002). The G ^∗ 01:04 allele and G ^∗ 01:04-G ^∗ 01:04 genotype emerged as protective, while the HLA-E ^∗ 01:03-HLA-E ^∗ 01:03 genotype may negatively impact disease prognosis. Conversely, the HLA-E ^∗ 01:01-HLA-E ^∗ 01:03 and HLA-E ^∗ 01:01-HLA-E ^∗ 01:01 genotypes may confer protection. Conclusion: Genetic variations in KIR, HLA-E, and HLA-G are associated with susceptibility and resistance to severe COVID-19 outcomes. This elucidates the intricate interplay of NK cells and immune-related genes, offering insights into potential therapeutic avenues and personalized approaches.

[This retracts the article DOI: 10.1155/2021/1736819.].

Macrophages play essential roles in homeostasis and disease, and they were considered terminally differentiated cells that cannot proliferate. However, growing evidence shows that macrophages can self-renew in homeostasis and multiple pathological states in vivo and artificial induction in vitro. With the rise of immune cell therapy based on macrophages, large-scale in vitro expansion of macrophages has become more and more urgent. However, the proliferation of macrophages in vitro is still inefficient because of the heterogeneity of macrophages, complicated crosstalk between macrophages and their microenvironments, and poor understanding of macrophage proliferation regulations. In this review, we summarized the discoveries known to stimulate macrophage proliferation in vitro, including cytokines, small molecule compounds, metabolites, the composition of pathogens and apoptotic cells, natural product extracts, gene editing, and other factors, as well as related mechanisms. It can be concluded that the promotion of macrophage proliferation in vitro covers various approaches and mechanisms. However, it is still necessary to test more strategies and learn more macrophage proliferation mechanisms to achieve large-scale engineering expansion of macrophages in vitro.

Background: The relationship between autoimmune diseases (AIDs) and cancer is unclear and this study aimed to investigate the relationship between AIDs and cancer at the genetic level using Mendelian randomization (MR). Methods: The study employed two-sample MR and meta-analysis to investigate the association between AIDs and 33 types of cancer, following STROBE-MR guidelines. Single nucleotide polymorphisms (SNPs) associated with AIDs were used as instrumental variables, with data from FinnGen, UK Biobank, and other databases. MR analyses included sensitivity checks, heterogeneity assessments, and reverse causality tests, using multiple MR methods (inverse-variance weighted (IVW), weighted median, MR-Egger, etc.). Meta-analysis was performed on validated results to confirm findings, with statistical analyses conducted using R software. Results: The results identified eight significant associations in both discovery and replication stages. Key findings include that myasthenia gravis (MG) significantly increases the risk of oral cavity cancer, multiple sclerosis (MS) is linked to increased risks of chronic lymphocytic leukemia (CLL) and small intestine cancer, and ulcerative colitis (UC) has mixed effects, reducing the risk of uterine cervix and larynx cancers, but increasing risks for pancreatic and bladder cancers. Meta-analysis confirmed eight secondary findings, highlighting pathogenic associations such as type 1 diabetes with esophagus cancer and protective effects like systemic lupus erythematosus (SLE) against acute myelocytic leukemia. Conclusions: This study provides evidence of a causal relationship between multiple AIDs and different cancer risks at the genetic level and provides a reference for the health management of patients with AIDs.

Bacterial lysate proteins (BLPs) serve as potential immunostimulants, recognized by pattern recognition receptors (PRRs) on immune cells, eliciting a robust immune response. In this study, THP-1 macrophages were treated with varying doses of BLPs derived from Streptococcus pyogenes (SP), Streptococcus agalactiae (SA), and Serratia marcescens (SM). The results showed significant increases (p  < 0.05) in pro-inflammatory cytokines such as TNF-α, IL-1β, IL-6, IL-12, granulocyte macrophage-colony stimulating factor (GM-CSF), eotaxin, and macrophage inflammatory protein (MIP)-1α, except for 5 µg of all BLPs for TNF-α and eotaxin, and 5 µg of SP for IL-12 production. No significant differences were found between the corresponding doses of SP and SA or SP and SM, except for GM-CSF in all doses, while SA and SM only showed a difference at the 5 µg dose for GM-CSF. Furthermore, there were no significant differences between the 10 and 20 µg doses of all BLPs, indicating that doses higher than 10 µg do not significantly enhance the pro-inflammatory response. Combination doses of SP + SM and SA + SM did not show significant differences, except for IL-1β, suggesting no synergistic effect. Cytotoxicity was observed to increase with higher BLP concentrations in a dose-dependent manner, with combinations of SP + SM and SA + SM exhibiting greater cytotoxicity than the individual BLPs. Proteomic analysis of BLPs identified immunostimulatory proteins, including heat shock proteins (HSPs; ClpB, DnaK, and GroEL), metabolic enzymes (glyceraldehyde 3-phosphate dehydrogenase (GAPDH), enolase, and arginine deiminase (ADI)), and surface and secreted proteins (ESAT-6-like protein, CRISPR-associated endonuclease Cas9, OmpA, porin OmpC, and serralysin), which are involved in immune modulation, bacterial clearance, and immune evasion. This study underscores the potential of bacterial proteins as vaccine adjuvants or supplementary therapies; however, further research is essential to find a balance between immune activation and inflammation reduction to develop safer and more effective immunostimulants.

Objective: This study aimed to analyze the relevant risk factors for nosocomial infection (NI) in patients who were admitted to an emergency department, explore the correlation between each influencing factor and the risk of NI, and evaluate the application value of immunological indicators on the patient prognosis, all of which can provide reference for clinical guidance. Methods: We prospectively enrolled 128 patients meeting the inclusion criteria who visited the emergency department of Dongzhimen Hospital, Beijing University of Chinese Medicine, from January 1 to December 31, 2019. Basic information and serum samples were collected from the patients, and flow cytometry was used. T lymphocyte subgroups, CD3⁺CD4⁺and CD3⁺CD8⁺, and natural killer (NK) cells were measured. Patients were divided into infection group and control group according to whether nosocomial infection occurred within 48 h of admission. Age, gender, type of disease, APACHE II score, Charlton score, T lymphocyte subtypes, and NK cell values were compared, and a logistic multivariate regression analysis was conducted. A multifactor regression analysis was performed on various risk factors. The nomogram website was used to draw a nomogram model of meaningful indicators, and the receiver-operating characteristic (ROC) curve was based on experimental results. Results: Logistics multivariate regression analysis showed the Charlton score and NK cell count were independent risk factors for nosocomial infection. Cell counts for subsets CD3⁺CD4⁺ and CD3⁺CD8⁺ were protective factors, and the OR value and 95% CI were 5.199 (1.933-13.983), 1.248 (1.055-1.475), 0.851 (0.790-0.916), and 0.832 (0.711-0.973), p < 0.05. respectively. Statistical significance was set at p < 0.05.The nomogram model suggested that the area under the curve for predicting the risk of nosocomial infection was 0.920 (0.872-0.967), p < 0.001. Conclusion: Patients with low CD3⁺CD4⁺ and CD3⁺CD8⁺ T lymphocyte or high NK cell count as well as high Charlton score are more likely to have nosocomial infection. Then, we speculate that the risk of nosocomial infection within 48 h is also high for patients with underlying diseases and immune function that is affected and suppressed on admission, regardless of whether infection occurs during hospitalization.

In recent years, a growing body of evidence has suggested a correlation between Hashimoto's thyroiditis (HT) and the onset and progression of papillary thyroid carcinoma (PTC). However, the mechanism underlying the relationship between HT and PTC remains incompletely understood. This review discusses the literature on the correlation between PTC and HT and summarizes the research concerning the immunological interplay between these two conditions. It also delves into tumor-associated cells (such as CD8+ T cells), tumor-associated macrophages (TAMs), regulatory T cells (Tregs), and cancer-associated fibroblasts (CAFs), alongside other tumor-associated factors, including interleukins (ILs), interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and hypoxia-inducible factor-1 (HIF-1), highlighting their roles in the interaction between PTC and HT. We also explore the strategic direction of immunotherapy in thyroid malignancies, particularly PTC with HT, and propose novel targeted immunotherapies for advanced thyroid cancer.

Lung adenocarcinoma (LUAD) is a prevalent and aggressive form of lung cancer with poor prognosis, largely due to late-stage diagnosis and limited therapeutic options. Recent studies suggest that long noncoding RNAs (lncRNAs) play critical roles in cancer progression and immune modulation, emerging as potential therapeutic targets. In this study, we investigated the expression and functional role of LINC00892 in LUAD using RNA sequencing data from The Cancer Genome Atlas (TCGA) and functional assays in vitro and in vivo. We found that LINC00892 is significantly downregulated in LUAD tissues compared to normal tissues, and lower LINC00892 expression correlates with poorer overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI), particularly in younger patients and those with early-stage disease. Bioinformatic analyses revealed that LINC00892 expression is positively correlated with immune cell infiltration, including CD4⁺ and CD8⁺ T cells, and negatively correlated with tumor-promoting Th2 cells, suggesting its role in shaping the tumor immune microenvironment. In vitro functional assays showed that LINC00892 overexpression inhibits LUAD cell proliferation, migration, and invasion while promoting apoptosis. Mechanistically, LINC00892 upregulation was found to suppress epithelial-mesenchymal transition (EMT) by increasing E-cadherin expression and decreasing levels of N-cadherin, vimentin, and slug. Additionally, in an in vivo mouse xenograft model, LINC00892 overexpression suppressed tumor growth and metastasis, accompanied by enhanced immune cell infiltration such as CD4⁺ and CD8⁺ T cells. Collectively, these findings suggest that LINC00892 acts as a tumor suppressor in LUAD by modulating immune infiltration and EMT, highlighting its potential as a prognostic biomarker and therapeutic target.