Journal of Immunology Research最新文献

Background: Hirschsprung's disease (HSCR) is a congenital enteric nervous system (ENS) disorder. Genetics cannot explain most sporadic cases. To explore the relationship between pathogen infection, autoantibodies, innate immune, and HSCR. Methods: Pathogen microarray was conducted in the serum of the prospective neonatal abdominal distension (NAD) cohort, consisting of 56 children followed for at least 6 months until the final diagnosis of HSCR was determined or excluded. We conducted an autoantibody microarray in an HSCR cohort, which is comprised of diagnosed HSCR patients (HSCR) and healthy control subjects (HC). RNA-seq of colon tissues from aganglionic and ganglionic segments of HSCR patients was performed. Results: Experimental results show that the serum lgM and lgG of enterovirus 71 (EV71) were significantly higher in HSCR than in the gastrointestinal dysfunction (GI) group, with a prediagnose value reaching area under the curve (AUC) over 0.76. We discovered that a group of autoantibodies were significantly higher in HSCR including neuronal pentraxin 1 (NPTX1), amyloid, neuron lysate, and myelin-associated oligodendrocytic basic protein (MOBP) than that in the HC group. These four autoantibodies could distinguish HSCR from the HC group, with a combined AUC of over 0.90 using both serum IgG and IgM. Further analysis showed that wide activation of innate immune pathways, including toll-like receptor (TLR) signaling pathway, neutrophil-to-lymphocyte ratio (NLR) signaling pathway, red cell distribution width to lymphocyte ratio (RLR) signaling pathway, and cyclic adenosine monophosphate (cAMP) signaling pathway in aganglionic compared to ganglionic segments of HSCR. Conclusion: This study suggested that virus-triggered autoimmunity may contribute to HSCR through activation of innate immunity, which facilitates the diagnosis and prevention of HSCR.

Objective: Doxorubicin (DOX) is an extensively used chemotherapeutic agent that induces cardiotoxicity. Studies have reported that exercise (EXE) can alleviate DOX-induced cardiotoxicity. Therefore, this study aimed to explore the mechanism by which EXE attenuates DOX-induced myocardial injury. Methods: In this study, cell and animal models of DOX-induced myocardial injury were constructed. The animal model was subjected to EXE intervention. Results: In this study, in vitro experiments revealed that miR-30d-5p negatively regulated polypeptide N-acetylgalactosaminyltransferase 7 (GALNT7) and that GALNT7 negatively regulated the expression of thyroid stimulating hormone receptor (TSHR). miR-30d-5p downregulated the expression of GALNT7, promoted the expression of TSHR, and promoted macrophage M1 polarization, thus aggravating cardiomyocyte injury. In vivo experiments revealed that EXE intervention significantly downregulated miR-30d-5p and TSHR expression, upregulated GALNT7, reduced inflammation, and promoted M2 macrophage polarization, thereby alleviating DOX-induced myocardial injury. In addition, overexpression of miR-30d-5p or knockdown of GALNT7 weakened the intervention effect of EXE, whereas overexpression of GALNT7 or knockdown of TSHR promoted the effect of EXE. Conclusion: EXE can modulate the miR-30d-5p/GALNT7 axis to inhibit the expression of TSHR, thereby regulating the polarization of macrophages to the M2 phenotype and ultimately alleviating DOX-induced myocardial injury, which provides new targets and strategies for the clinical treatment of myocardial injury.

Malignant tumors, characterized by uncontrolled cell proliferation, are a leading global health challenge, responsible for over 9.7 million deaths in 2022, with new cases expected to rise to 35 million annually by 2050. Immunotherapy is preferred to other cancer therapies, offering precise targeting of malignant cells while simultaneously strengthening the immune system's complex responses. Advances in this novel field of science have been closely linked to a deeper knowledge of tumor biology, particularly the intricate interplay between tumor cells, the immune system, and the tumor microenvironment (TME), which are central to cancer progression and immune evasion. This review offers a comprehensive analysis of the molecular mechanisms that govern these interactions, emphasizing their critical role in the development of effective immunotherapeutic products. We critically evaluate the current immunotherapy approaches, including cancer vaccines, adoptive T cell therapies, and cytokine-based treatments, highlighting their efficacy and safety. We also explore the latest advancements in combination therapies, which synergistically integrate multiple immunotherapeutic strategies to overcome resistance and enhance therapeutic outcomes. This review offers key insights into the future of cancer immunotherapy with a focus on advancing more effective and personalized treatment strategies.

B cells are essential for humoral immune response due to their ability to secrete antibodies. The development of B cells from the bone marrow to the periphery is tightly regulated by a complex set of immune signals, and each subset of B cells has a unique metabolic profile. Mitochondria, which serve as cellular energy powerhouses, play an essential role in regulating cell survival and immune responses. To maintain metabolic homeostasis, mitochondria dynamically adjust their morphology, distribution, and mass via biogenesis, fusion and fission, translocation, and mitophagy. Despite its extreme importance, the role of mitochondrial quality control (MQC) in B cells has not been thoroughly summarized, unlike in T cells. This article aims to review the mechanism of MQC that shapes B cell fate and functions. In addition, we will discuss the physiological and pathological implications of MQC in B cells, providing new insights into potential therapeutic targets for diseases associated with B cell abnormalities.

Background: Respiratory tract infections are a common health problem. Cytokines/chemokines play a critical role in the regulation of the immune system. Their defective production may predispose to recurrent respiratory tract infections (RRIs), and an excessive immune response may lead to chronic inflammation and cause damage to the respiratory tract. Another biomarker of respiratory infections may be immunoglobulin-IgG4. Its meaning has still been little explored. We wanted to assess the suitability of the levels of biomarkers tested: interleukin (IL)-17A, IL-18, IL-23, normal T cells expressed and secreted (RANTES), and induced protein (IP)-10, as well as immunoglobilun G4 (IgG4) to predict recurrent infections. Methods: The study group (SG) included a total of 130 children (68 girls, 62 boys) between 3 and 17 years of age with RRI. The control group (CG) included 86 healthy children with no symptoms of inflammatory or allergic diseases (44 girls and 42 boys) of the same age. Blood samples were collected in fasting state and then serum samples were frozen and stored until biomarker assay. Results: Serum RANTES, IL-18, IL-23, and IgG4 concentration were higher in all children with recurrent infections vs. those in the CG (p  < 0001). Serum levels of IL-17A and IP-10 were also significantly higher in the SG than in the CG, but only in the youngest children. Among the six serum markers, RANTES demonstrated the highest area under the receiver operating characteristic curve (area under curve) value (0.998, 95% confidence interval [CI]: 0.98-1.0, p < 0.001) for the diagnosis of RRIs, followed by IL-23 (0.99, 95% CI 0.966-0,999, p < 0.001) and IL-18 (0.957, 95% CI 0.921-0.980, p < 0.001). Conclusions: RANTES, IL-23, and IL-18 could be strong predictors of respiratory infections recurrence in children.

Methods: We sourced genetic association data from public genome-wide association study databases for populations of European ancestry. Adhering to MR principles, we identified valid instrumental variables from genetic variants. A range of statistical methods were applied for MR analysis, with the inverse variance weighted (IVW) method emerging as the most reliable estimator of causality in this context.

Results: The causal estimates obtained using the IVW method revealed a significant association between genetically predicted AA and rheumatoid arthritis (RA; OR = 1.06, 95% CI = 1.01-1.12, P=0.029). Conversely, genetically predicted RA showed nonsignificant causal estimates of AA (OR = 0.97, 95% CI = 0.92-1.02, P=0.204). Additionally, there was no evidence to suggest that AA may increase the risk of inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC), systemic lupus erythematosus (SLE), and psoriasis (PSO). The sensitivity analysis confirmed the absence of heterogeneity or horizontal pleiotropy effects.

Conclusion: Our findings shed light on the causal effects between genetically predisposed AA and RA. They also suggest the potential clinical utility of human leukocyte antigen (HLA) risk genetic markers for developing personalized treatment and prevention strategies.

Oxidative stress is crucial in ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC). Intestinal epithelial cells (IECs) are an important component of the intestinal barrier. In previous studies, we have demonstrated that suppressing microRNA-222-3p (miR-222-3p) can protect against oxidative stress in IECs, which ameliorates colonic injuries in UC mice and prevents the conversion of UC to CAC. In this case, we hope to explore whether moxibustion can alleviate UC and CAC by inhibiting miR-222-3p based on mouse models of UC and CAC. After herb-partitioned moxibustion (HPM) intervention, the disease activity index (DAI) and colon macroscopic damage index (CMDI) were significantly reduced in UC mice, and the number and volume of intestinal tumors were decreased considerably in CAC mice. Meanwhile, we found that HPM suppressed miR-222-3p expression and upregulated the mRNA and protein expression of Brahma-related gene 1 (BRG1), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), while inhibiting Kelch-like ECH-associated protein 1 (Keap1) expression in IECs of UC and CAC mice. With changes in reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and inflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α), we verified that HPM protects against oxidative stress and inflammation in IECs of UC and CAC mice. The effect of HPM was inhibited in miR-222-3p overexpression mice, further demonstrating that the protective effect of HPM on UC and CAC mice was through inhibiting miR-222-3p. In summary, HPM regulates the BRG1/Nrf2/HO-1 pathway by inhibiting miR-222-3p to attenuate oxidative stress in IECs in UC and CAC.

Understanding the immune response generated by SARS-CoV-2 is critical for assessing efficient therapeutic protocols and gaining insights into the durability of protective immunity. The current work was aimed at studying the specific humoral responses against SARS-CoV-2 in Cuban COVID-19 convalescents. We developed suitable tools and methods based on ELISA methodology, for supporting this evaluation. Here, we describe the development of an ELISA for the quantification of anti-RBD IgG titers in a large number of samples and a similar test in the presence of NH₄SCN as chaotropic agent for estimating the RBD specific antibody avidity. Additionally, a simple and rapid ELISA based on antibody-mediated blockage of the binding RBD-ACE2 was implemented for detecting, as a surrogate of conventional test, the levels of anti-RBD inhibitory antibodies in convalescent sera. In a cohort of 273 unvaccinated convalescents, we identified higher anti-RBD IgG titer (1 : 1,330, p  < 0.0001) and higher levels of inhibitory antibodies blocking RBD-ACE2 binding (1 : 216, p  < 0.05) among those who had recovered from severe illness. Our results suggest that disease severity, and not demographic features such as age, sex, and skin color, is the main determinant of the magnitude and neutralizing ability of the anti-RBD antibody response. An additional paired longitudinal assessment in 14 symptomatic convalescents revealed a decline in the antiviral antibody response and the persistence of neutralizing antibodies for at least 4 months after the onset of symptoms. Overall, SARS-CoV-2 infection elicits different levels of antibody response according to disease severity that declines over time and can be monitored using our homemade serological assays.

Materials and methods: Using flow cytometry, we identified and quantified Group 2 innate lymphocytes, T helper 2 cells, follicular helper T cells, and T helper 17 cells in peripheral blood samples from 49 individuals with asthma. We then conducted cross-sectional analyses to assess relationships between levels of these immune cells and lung function parameters, including the percentage predicted forced expiratory volume in 1 s (%FEV1). We also examined correlations between the proportions of immune cells and type 2 biomarkers.

Results: Proportions of CXCR5⁺ follicular helper T cells in human peripheral blood, as opposed to Group 2 innate lymphoid cells (ILC2) or T helper 2 cells, were significantly higher in cases with %FEV1 < 80% compared to those with %FEV1 ≥ 80%. Further, these proportions correlated negatively with %FEV1 and positively with blood eosinophil counts.

Conclusions: The proportion of circulating follicular helper T cells, but not T helper 2 cells or Group 2 innate lymphoid cells, may reflect the presence of airway obstruction caused by persistent type 2 inflammation.