Critical Reviews in Immunology最新文献

Sensorineural hearing loss (SNHL) seriously affects people's lives, and the degradation of spiral ganglion neurons (SGNs) is the main cause of SNHL. Many studies have revealed that long non-coding RNAs (lncRNAs) are linked to SGNs. However, it is still unclear how lncRNAs affect damage repair in SGNs. Fluorescence in situ hybridization (FISH) and nuclear-cytoplasmic separation (NCS) assays were used to verify the cellular localization of lncRNA-HOTAIR in SGNs. Primary SGNs were dissected from the C57BL/6J male mice. We constructed sh-HOTAIR SGNs to investigate the role of HOTAIR. Target gene levels were analyzed using qRT-PCR and Western blot assays. Additionally, SGN proliferation was assessed using the CCK-8 and flow cytometry assays. Moreover, RIP and dual-luciferase assays were conducted to elucidate the interactions among HOTAIR, miRNA, and mRNA. Our findings illustrated that HOTAIR was primarily expressed in the cytoplasm, and downregulation of HOTAIR increased SGN apoptosis by approximately 30% (P < 0.001). In addition, miR-211-5p was identified as being directly downstream of HOTAIR, which could bind with miR-211-5p to modulate SGNs growt (all P < 0.05). Furthermore, miR-211-5p reduced the proliferation of SGNs (P < 0.001) and increased apoptosis (P < 0.01) by binding to the 3'-UTR of EYA3, whereas overexpression of EYA3 reversed this result (all P < 0.05). Our findings suggest that HOTAIR promotes SGN proliferation by competitively binding to miR-211-5p and regulating EYA3 expression, highlighting its potential as a novel target for sensorineural hearing loss therapies.

Genetic polymorphisms in genes that enable the production of an effective host immune response, such as single nucleotide polymorphisms (SNPS) in the IL-6, INF-alpha, IFN-gamma, IL-10, TGF-beta genes can cause unfavorable clinical conditions or susceptibility to pathologies. The objective of this work is to evaluate the epidemiological and genetic profile of professionals from health institutions during the first pandemic wave. A case-control study was performed with convenience sampling from health institutions (HI) workers from Belém-PA, Northern Brazil (N = 213), divided into symptomatology groups (Asymptomatic-AS, n = 91; and Symptomatic-SI, n = 122); and severity groups classified by chest computerized tomography-CCT data (symptomatic with pulmonary involvement-SCP, n = 37; symptomatic without pulmonary involvement-SSP, n = 8). Genotyping was performed by sanger sequencing for SNP TNF-α -308 G/A (rs1800629), IFN-γ +874 T/A (rs2430561), TGF-β codon 10 (rs1982073), codon 25 (rs1800471), IL-6 - 174 G/C (rs180079), IL-10 - 1082 A/T (rs1800896), -819 C/T (rs1800871), and -592 A/C (rs1800872), and statistical analysis through the Epilfo program. Significant association was observed between the presence of comorbidities and poor prognosis of COVID-19 (especially between COVID-19 and overweight and obesity). Only the TNF-α 308 G/A snp was significantly associated with the symptoms and severity of COVID-19. These findings about this TNF-α SNP passed in the multiple testing correction at a false discovery rate (FDR)< 0.05. These data can help medicine and the scientific community understand the influence of genetics and epidemiological parameters in combating COVID-19.

Neonatal candidiasis poses significant clinical challenges due to its potential for severe morbidity and mortality in vulnerable infants. Due to their underdeveloped immune system, neonates are at a higher risk for infections caused by Candida species. They can vary from mild to severe, including penetrating deep tissues, bloodstream spread, and dissemination to organs. The immune system of newborns is marked by a limited innate immune response, with lower levels of pro-inflammatory cytokines. Adaptive immunity, important for lasting protection, also experiences delayed maturation with weakened Th1 and Th17 responses. These shortcomings result in a higher vulnerability to Candida infections during infancy. Murine models have been crucial in understanding the reasons behind this susceptibility. These models assist in examining how different immune elements, like neutrophils, macrophages, and T cells, and their interactions are involved in Candida infections. Moreover, they offer an understanding of how early-life exposure to Candida affects immune responses and may aid in developing possible therapeutic plans. In this article we review current results from research to provide a thorough summary and critical insights into neonatal immune response to Candida, highlighting the importance of using murine models in this field of study. Understanding these immune dynamics is essential for creating specific treatments and preventive strategies to prevent newborns from Candida infections, ultimately improving neonatal health outcomes.

High-grade glioma tumors are the common cause of death in pediatric patients. K27M cell line is regularly used as tumor model to study diffuse intrinsic pontine glioma (DIPG) since they harbor genetic mutation in which the lysine of the histone H3 protein is replaced with a methionine. The objective of this study is to demonstrate the significance of supercharged NK (sNK) cells alone or in combination with ONC201 or ONC206 to target such aggressive pediatric brain tumor K27M. We have observed increased secretion of IFN-γ by sNK cells compared to primary IL-2-activated NK cells. Combining sNK cells with ONC201 or ONC206 further increased IFN-γ in sNK cells. When primary NK cells and sNK cells were used as effectors against the glioma tumor cell line K27M, tumor cells were found to be highly susceptible to sNK cell-mediated cytotoxicity compared to primary NK cell-mediated cytotoxicity. sNK cell-mediated cytotoxicity against K27M was significantly increased when sNK cells were combined with ONC201 and ONC206. This study suggests the potential use of sNK cells alone or in combination with ONC201 or ONC206 as therapeutic strategies in treating and preventing the recurrence of aggressive pediatric brain tumors.

An increase in the number of natural killer (NK) cells in the lungs can be observed in chronic obstructive pulmonary disease (COPD). Immune-related genes (IRGs) play a crucial role in the differentiation of NK cells; however, the expression of IRGs and the possible regulatory mechanisms involved in COPD remain unclear. Single-cell RNA sequencing (scRNA seq) data of lung tissue of COPD patients were analyzed to screen NK cell cluster marker genes obtained in the ImmPort database. IRG activity in NK cell differential genes was calculated using the AUCell package. Analysis of batch sequencing datasets of biopsy tissue under COPD bronchoscopy to explore common IRGs in patients with COPD was conducted. Relevant regulatory transcription factors (TFs) were identified from the human TFDB data-base. Protein-protein interaction (PPI) networks for key TFs were generated by STRING database. A total of 12 different cell types were identified, among which the number of NK cells in COPD patients increased significantly. Gene-set enrichment analysis showed that immune response pathway was significantly enriched based on differentially expressed genes (DEGs) in NK cells. We found 55 co-expressed common IRGs and 43 co-expressed TFs in scRNA sequencing data and bulk RNA sequencing data. The PPI network indicates that EGR1, JUN, and FOS are hub TFs. In conclusion, we suggest that NK cells may be involved in chronic airway inflammation in COPD patients through bioinformatics analysis of scRNA and bulk RNA sequencing data. Specifically, EGR1 may participate in the transcriptional regulation of IRGs in NK cells, with potential involvement of calcium signaling and TGF-β/Smad pathways.

Calcineurin inhibitors (CNIs) are key in immunosuppressive therapy for organ transplantation and autoimmune diseases by modulating T cell activation. This review details how CNIs inhibit T cell receptor signaling, cytokine production, and T cell differentiation by binding to intracellular proteins, thus preventing the activation of NFAT, a critical transcription factor. The clinical benefits of CNIs include preventing graft rejection and controlling autoimmune responses, but they also have significant side effects such as nephrotoxicity, neurotoxicity, hypertension, hyperlipidemia, and increased risk of infections and malignancies. Optimizing CNI use involves developing safer versions, personalizing regimens, and combining therapies to lower doses and reduce side effects. Understanding CNIs' interactions with T cells can improve therapy outcomes and guide the creation of targeted treatments. Effective patient monitoring and management are essential to mitigate toxicities. Future research should focus on CNIs' pharmacodynamics and pharmacokinetics in developing next-generation immunosuppressants, and personalized and combination therapies to enhance safety and efficacy, ultimately improving patient outcomes and quality of life.

Immunotherapy has transformed cancer treatment by leveraging the immune system to target and destroy cancer cells. This scoping review synthesizes recent data on the clinical outcomes and quality of life (QoL) impacts of key immunotherapy agents, including checkpoint inhibitors (e.g., pembrolizumab, nivolumab) and CAR T-cell therapies. A systematic search in PubMed and Google Scholar identified primary studies published in the past five years (2020-2024) focusing on clinical efficacy and QoL metrics. Findings reveal that immunotherapy offers notable survival benefits and QoL improvements, especially in hematologic cancers, where CAR T-cell therapies demonstrate high efficacy in relapsed or refractory cases. However, challenges remain in extending these benefits to solid tumors, with common obstacles being immune-related toxicities and limited access. Promising new strategies, such as CAR NK cells and combination regimens, are under investigation to enhance safety and applicability to solid tumors. Critical factors influencing outcomes include patient-specific elements like genetic mutations, age, and variability in clinical trial demographics, which affect both efficacy and QoL. As immunotherapy advances, personalized treatment approaches informed by genetic and clinical profiles will be crucial for optimizing results. Further research should address toxicity reduction, broaden target options, and develop accessible off-the-shelf therapies. This review underscores immunotherapy's impact on survival and QoL, advocating for precision medicine in oncology to enhance patient-centered outcomes.

Galectin-10(Gal-10)/CLC(Charcot-Leyden crystal) has been discovered to be related to ECRSwNP characterized by high eosinophilic infiltration. We aimed to investigate the effects of Gal-10 on ECRSwNP. A total of 36 tissue samples were collected, including 11 ECRSwNP samples, 15 non-ECRSwNP samples, and 10 Control samples. Human eosinophils were divided into 3 groups: Control, siRNA-NC, and Gal-10 interference groups. Immunohistochemistry (IHC), Western blotting and quantitative real-time PCR (qRT-PCR) detected the expression of Gal-10 in the tissues samples and expression of p-p38 and p-p65 in human eosinophils. Enzyme-Linked Immunosorbent Assay (ELISA) was adopted to measure the expression levels of IL-4, IL-5, IL-8, MBP, ECP, and TNF-α in the human eosinophils. We found the expression of Gal-10 was significantly higher in ECRSwNP group (P < 0.05). The expression levels of IL-4, IL-5, IL-8, MBP and TNF-α in the Gal-10 interference group were lower (P < 0.05), but ECP had no statistical difference in human eosinophils. There showed the expression levels of p-p38 and p-p65 proteins in the Gal-10 interference group were lower (P < 0.05). The deletion of Gal-10 in eosinophils down-regulates the expression of cytokines and granule cationic proteins in ECRSwNP which may be caused by the p38MAPK/ NF-κB pathway.

The present study investigated the expression of miR-598 in both breast cancer tissues and cells. Overexpression systems were established by introducing miR-598 mimics and pcDNA- Fibroblast Growth Factor Receptor 2(FGFR2) plasmids, either individually or in combination, into breast cancer cells. Four groups were constituted for probing purposes: control group, miR-598 mimics group, pcDNA-FGFR2 group, and mimics+FGFR2 group. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to measure the expression of miR-598 and FGFR2. Furthermore, bioinformatics software was used to predict and identify the possible binding sites between miR-598 and FGFR2. To validate the predicted binding sites, a dual-luciferase reporter gene experiment was carried out. A clone formation assay was used to evaluate cell proliferation, while glucose consumption and lactic acid production assays were conducted using a kit. Moreover, Western blot analysis was done to ascertain the expression of Bcl-2, Bax, Caspase-3, and Caspase-9 proteins. The expression of miR-598 in breast cancer tissues and cell lines was found to be significantly lower than that in normal breast tissues and cell lines, respectively (P < 0.05). It was also revealed that FGFR2 is the target gene of miR-598 and there is an inverse correlation between the two. Overexpression of miR-598 led to a decrease in clonal formation rate caused by high FGFR2 levels. Moreover, the overexpression of miR-598 reversed the effects induced by high FGFR2 levels, such as increased mitochondrial membrane potential and reduced expression of apoptosis-associated proteins. The microRNA miR-598 has been found to decrease the proliferation of breast cancer cells by targeting FGFR2, inducing apoptosis, and suppressing glucose consumption.

Alzheimer's disease (AD) is a global neurodegenerative disorder characterized by progressive cognitive decline. Its core pathology involves neurofibrillary tangles mediated by hyperphosphorylated tau protein and senile plaques formed by extracellular deposits of β-amyloid. As the global incidence of AD continues to rise, human health faces a serious threat. However, the complexity of its pathogenesis poses significant challenges to current prevention and treatment strategies. Recent studies reveal that T cells, as key components of the adaptive immune system, exhibit abnormalities in both quantity and function within the brains of AD patients. They infiltrate brain parenchyma through multiple pathways-including the blood-brain barrier, choroid plexus, and meningeal lymphatics-and are deeply involved in AD pathology. In this review, we first introduce recent discoveries in the pathogenesis of AD, including tau protein, β-amyloid plaques, and neuroinflammation. We then describe the immune mechanisms and infiltration pathways of T cells in AD. Finally, we focus on the mechanisms by which different T cell subtypes contribute to brain damage in AD, aiming to provide a theoretical foundation for developing AD therapies guided by neuroimmune homeostasis.