Search Results (300)

Asthma is a chronic and multifaceted respiratory condition that affects over 300 million individuals across the globe. It is characterized by persistent inflammation of the airways, which leads to episodes of wheezing, breathlessness, chest tightness, and coughing. The most prevalent form of asthma is classified as Type 2 or T2-high asthma. In this variant, the immune response is heavily driven by eosinophils, mast cells, and T-helper 2 (Th2) cells. These components release a cascade of cytokines, including interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13). This release promotes several processes: the production of immunoglobulin E (IgE), which is integral to allergic responses; the recruitment of eosinophils—white blood cells that contribute to inflammation and tissue damage. Conversely, non-Type 2 or T2-low asthma is typically associated with a different inflammatory profile characterized by neutrophilic inflammation. This type of asthma is driven by T-helper 1 (Th1) and T-helper 17 (Th17) immune responses, which are often present in older adults, smokers, and those suffering from more severe manifestations of the disease. Among asthmatic patients, approximately 80–85% of cases are classified as T2-high asthma, while only 15–20% are T2-low asthma. Treatment of asthma focuses heavily on controlling inflammation. Inhaled corticosteroids remain the cornerstone therapy for managing T2-high asthma. For more severe or treatment-resistant cases, biologic therapies targeting specific inflammatory pathways, such as anti-IgE (omalizumab), anti-IL-5 (mepolizumab, benralizumab), and anti-IL-4/IL-13 (dupilumab), have shown great promise. For T2-low asthma, macrolide antibiotics like azithromycin and other novel therapies are being explored. This article reviews the safety, efficacy, and indications of the currently approved biologics and discusses potential novel biologics for asthma. Full article

Numerous scientific findings indicate that excess adipose tissue, particularly visceral fat, is associated with a chronic inflammatory state manifested by elevated levels of proinflammatory cytokines and an imbalance in the T helper type 1/type 2 (Th1/Th2) response, which carries numerous metabolic consequences. Obesity induces, among other effects, the activation of the kynurenine pathway and a reduction in serotonin synthesis, alterations in adipokine profiles, modifications of the hypothalamic–pituitary–adrenal (HPA) axis, disturbances in fatty acid ratios, oxidative stress, and dysfunction of the gamma-aminobutyric acid (GABA)ergic system. These neuroimmunological and metabolic disturbances, along with obesity-induced neurotransmission abnormalities that may represent a common underlying model of depression, could provide valuable insights into the pathomechanisms of depression, allowing for prediction of disease progression and individualized therapeutic strategies in overweight patients. Furthermore, the analysis of inflammation-associated biomarkers opens up new therapeutic perspectives, suggesting that interventions aimed at reducing inflammation might lead to potential advances in the treatment of depression. Full article

Background: Allergic rhinitis (AR) is triggered by immunoglobulin E (IgE)-mediated immune responses to airborne allergens. Recent studies highlight the pivotal role of T follicular helper 2 (Tfh2) cells in IgE production. Interleukin-37 (IL-37) has emerged as an intrinsic modulator of innate immunity and inflammatory processes. We aimed to investigate the regulatory effect of IL-37 on Tfh2 cells in the pathogenesis of AR. Methods: Blood samples were collected from AR patients and controls. The IL-37 levels and the frequency of Tfh2 cells were detected by enzyme-linked immunosorbent assay (ELISA) and flow cytometry, respectively. The isolated Tfh2 cells were cultured or cocultured with naive B cells. The regulatory effects of IL-37 on Tfh2/B cells were assessed using ELISA, quantitative real-time polymerase chain reaction (qRT-PCR). Mouse models of ovalbumin (OVA)-induced AR were established to explore the effect of IL-37 in vivo. Results: IL-37 suppressed the production of IL-4 and IL-21 by Tfh2 cells and downregulated C-X-C chemokine receptor type 5 (CXCR5) and B-cell lymphoma 6 protein (Bcl6) mRNA expression while upregulating B lymphocyte-induced maturation protein 1 (Blimp1) and signal transducers and activators of transduction5 (STAT5) mRNA. IL-37 decreased IgE production by B cells significantly, and the addition of anti-IL-18 receptor α alleviated this effect. In mouse models, IL-37 reduced nasal rubbing, sneezing, eosinophil counts, OVA-specific IgE, and Tfh2 proportions. Conclusions: IL-37 plays a crucial role in modulating Tfh2 cell responses in AR, suggesting a potential therapeutic target for this condition. Full article

This study investigated the effect of Codium fragile (WCF) water extract in reducing allergic inflammation in ovalbumin (OVA)-induced mice. Mice were sensitized to OVA + aluminum hydroxide, administered WCF for one week, and exposed to 1% aerosolized OVA. As a result, WCF intake reduced the OVA-induced increase in CD4⁺ T cells, CD8⁺ T cells, the T helper type 2 (Th2)/T helper type 1 (Th1) cell ratio, and inflammatory cells such as eosinophils and lymphocytes. Furthermore, WCF reduced Th2 cytokines such as interleukin (IL)-5, IL-13, and IL-33 and inflammatory cytokines such as tumor necrosis factor α (TNF-α) and IL-1β in lung tissues. A histological analysis showed that WCF intake decreases OVA-induced pulmonary inflammation, bronchial wall thickness, and mucus score and increases pulmonary alveolar area. Moreover, WCF inhibited the nuclear factor κB (NF-κB) pathway, the transforming growth factor β (TGF-β)/Smad pathway, and apoptosis-related proteins in lung tissues that OVA excessively activated. The oleamide (9-octadecenamide) content, representing a physiologically active component of WCF, was analyzed and validated using a high-performance liquid chromatography-photodiode array (HPLC-PDA) system. These results demonstrate that WCF may serve as a potential preventive agent for respiratory dysfunction such as allergic asthma by suppressing NF-κB and TGF-β/Smad pathways. Full article

Background: Primary cutaneous peripheral T-cell lymphoma, not otherwise specified (pcPTCL-NOS), is a rare and aggressive form of lymphoma. Its characteristics and treatment outcomes remain poorly understood. Methods: We identified 15 patients who were diagnosed with pcPTCL-NOS between January 2014 and August 2024 at Tianjin Medical University Cancer Institute and Hospital (TMUCIH) in this retrospective study. The clinical and immunophenotypic features, treatment regimens, and outcomes of these patients were investigated. Results: All patients (4 men, 11 women; median age 54 years) presented with skin lesions, including five stage T1, four stage T2 and six stage T3 lesions. pcPTCL-NOS manifests clinically either with solitary or disseminated rapidly growing nodules/tumors and papules and, less often, ulcers. The lesion sites in patients presenting with solitary/localized tumors (stage T1 and T2) were the head and limbs, and those in patients presenting with disseminated lesions (stage T3) were the trunk, head, and limbs. The CD4/CD8 immunophenotypic characteristics were as follows: CD4+/CD8− 53.33%; CD4+/CD8+ 26.67%; CD4−/CD8− 13.33%; and CD4−/CD8+ 6.67%. One patient had a T follicular helper (TFH) phenotype. Five patients had aberrant expression of the B-cell marker CD20 by tumor cells. All patients received CHOP or CHOP-like regimens as the initial treatment, with three patients undergoing complete lesion resection before chemotherapy, seven patients receiving treatment combined with chidamide (tucidinostat), two patients receiving treatment combined with brentuximab vedotin, two patients receiving treatment combined with mitoxantrone liposomes (Lipo-Mit), three patients receiving treatment combined with radiotherapy, and two patients receiving ASCT after the first-line treatment. The OS rates at 1 year, 2 years, and 3 years were 80%, 77.8%, and 77.8%, respectively; the PFS rates were 60%, 44.4%, and 33.3%, respectively. With a median follow-up of 40 months, the median PFS was 21 months, and the median OS was not reached. Univariate analyses revealed that patients with B symptoms and the CD4−/CD8− phenotype had inferior outcomes (p < 0.05). Age, sex, tumor stage, PIT score, Ki-67 index, elevated β2-MG levels, expression of CD20 or PD1, and treatment selection were not associated with the prognosis. A trend of a survival benefit in patients with solitary (T1) tumors compared with patients with disseminated (T2, T3) tumors was observed, suggesting that it is possible to reduce the intensity of treatment in patients with T1 tumors in the future. Conclusions: pcPTCL-NOS is an aggressive but poorly characterized lymphoma that may require early and active systemic treatment. However, for patients with T1 tumors, reducing the intensity of treatment with CHOP should be appropriately considered. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by epidermal barrier dysfunction and immune dysregulation, with interleukin (IL)-4, IL-13, and IL-31 recognized as key mediators. Prurigo nodularis (PN) is another chronic inflammatory disorder driven by T helper type 2-mediated inflammation and neural dysregulation, leading to severe pruritus. Nemolizumab, a humanized monoclonal antibody targeting IL-31 receptor A, has been approved for use in the treatment of AD and PN. Clinical trials have demonstrated significant reductions in pruritus and cutaneous symptoms associated with its use. In clinical practice, acute eczema and edematous erythema frequently occur, occasionally necessitating the discontinuation of treatment. Despite these observations, no comprehensive review has examined nemolizumab-associated cutaneous adverse events. This review aimed to examine various cutaneous reactions associated with nemolizumab therapy, including psoriasiform eruptions, AD exacerbation, bullous pemphigoid, drug-induced eruptions, and fungal infections. Potential mechanisms underlying these reactions include T-cell activation due to drug sensitization, immune responses triggered by nemolizumab acting as a hapten, and a relative increase in IL-4 and IL-13 levels following IL-31 inhibition. However, the precise pathophysiological mechanism and risk factors remain unclear, and standardized clinical management guidelines are lacking. Further accumulation of clinical data and immunological research are essential for developing evidence-based strategies to manage these adverse events, ensuring treatment continuity and optimizing patient outcomes. Full article

Vitamin D has been shown to improve immunity as well as vascular function. We investigated the effect of cholecalciferol on T-cell phenotype in cultured peripheral blood mononuclear cells (PBMCs) from twenty vitamin D-deficient, non-diabetic chronic kidney disease (CKD) subjects. We also studied vitamin D effects on endothelial and vascular function markers in human aortic endothelial cells (HAECs) and in human aortic smooth muscle cells (HASMCs), respectively. We studied endothelial nitric oxide synthase (eNOS), mitogen-activated protein kinase 38 (p38 Map kinase), protein kinase B (Akt), and nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) in HAECs and α-smooth muscle actin (α-SMA), smooth muscle calponin (SM-Calponin), smooth muscle myosin heavy chain (SM-MHC), and calcium-sensing receptor (CaSR) in HASMCs. Vitamin D receptors (VDRs) and CYP27B1 were studied in both cell types. In cultured PBMCs isolated from CKD subjects, the percentage of T helper 1(TH1) cells significantly decreased while that of T helper 2 (TH2) cells increased after cholecalciferol treatment. No significant change in intracellular and surface markers of T helper 17 (TH17) and T regulatory (Treg) cells was observed. In vitro treatment of HASMCs and HAECs with cholecalciferol led to significant and favorable alterations in mRNA expression of markers of vascular smooth muscle cells, i.e., α-SMA, SM-Calponin, and SM-MHC. Regarding endothelial cell markers, mRNA encoding eNOS, p38 Map kinase, protein kinase B (Akt), NADPH oxidase, VDR, and CYP27B1 were also significantly changed. Finally, the expression levels of the following proteins were notably altered: NADPH oxidase and protein kinase B (Akt) (in HAECs); SM-MHC and SM-Calponin (in HASMCs). In vitro treatment of PBMCs with cholecalciferol led to a favorable change in T-cell population, decreasing TH1 and increasing TH2 cell percentage, along with beneficial alterations in mRNA expression of HASMCs and HAECs’ cell markers. This study provides evidence that cholecalciferol can influence immune and vascular function in CKD. Full article

An increase in immunoglobulin G4 (IgG4) levels is typically associated with immunological tolerance states and develops after prolonged exposure to antigens. Accordingly, IgG4 is considered an anti-inflammatory antibody with a limited ability to trigger efficient immune responses. Additionally, IgG4 reduces allergic reactions by blocking immunoglobulin E (IgE) activity. In the case of COVID-19, it has been reported that the repeated administration of some vaccines induces high IgG4 levels. The latest research data have revealed a surprising IgE anti-receptor binding domain response after both natural infection and several SARS-CoV-2 vaccines. The presence of IgG4 and IgE in COVID-19 disease suggests that the virus may induce an “allergic-like” response to evade immune surveillance, leading to a shift from T helper 1 (Th1) to T helper 2 (Th2) cells, which promotes tolerance to the virus and potentially contributes to chronic infection. The spike protein from vaccines could also induce such a response. Interestingly, “allergen-like” epitopes and IgE responses have been reported for other viruses, such as influenza, human immunodeficiency virus (HIV), and respiratory syncytial virus (RSV). The impact of this viral-induced tolerance will be discussed, concerning long COVID and the protective efficacy of vaccines. Full article

(1) Background: Clinical evidence has raised concerns regarding a potential link between COVID-19 mRNA-based vaccines and the occurrence of thromboembolic events. So far, no research has explored the effects of this possible interaction in cancer patients undergoing active treatment. We leveraged prospective monitoring from the Vax-On-Third-Profile study to examine the development of venous thromboembolism (VTE) after the third dose of mRNA-BNT162b2 (tozinameran) and its association with antibody and lymphocyte responses. (2) Methods: Patients who had received a third dose of tozinameran and had not experienced any VTE in the previous 30 days were eligible. A serological evaluation was conducted before the booster vaccination (timepoint-1) and four weeks thereafter (timepoint-2) to measure antibody titers against the SARS-CoV-2 spike protein, as well as to determine the absolute counts of T-helper cells, T-cytotoxic cells, B cells, and NK cells. Data were acquired from November 2021 to October 2022 and analyzed from November 2022 to October 2023. (3) Results: The present study involved 429 patients who were given a third dose of tozinameran from 26 September to 30 October 2021. Among the active treatments of interest, 109 (25.4%) patients received targeted therapy, 111 (25.9%) received cytotoxic chemotherapy, 39 (9.1%) received immune checkpoint inhibitors, 21 (4.9%) received endocrine therapy, and 30 (7.0%) received a combination of chemotherapy and targeted agents in the eight weeks preceding the booster dosing. In addition, 119 (27.7%) patients who had discontinued any systemic therapy for at least 12 weeks accounted for the reference subgroup. After a median follow-up time of 10.6 (95% CI 8.1–11.7) months, we observed 31 venous thromboembolic events in the general population, for an overall incidence rate of 7.2% (95% CI 5.0–10.1). The median time to VTE development after booster immunization was 99 (95% CI 85–112) days. In a univariate comparison, patients exposed to targeted therapies (11.3% [95% CI 6.0–18.9]; p = 0.030) or immune checkpoint inhibitors (16.2% [95% CI 6.2–32.0]; p = 0.012) had a significantly higher incidence of VTE than the reference cohort (3.4% [95% CI 0.9–8.5]). Univariate analysis of immune responses showed that only dynamic changes pertaining to NK cell distributions correlated significantly with VTE occurrence. Multivariate regression analysis confirmed only a high-level NK cell response (OR 6.10 [9% CI 2.16–17.21]; p = 0.001), a history of thromboembolic events (OR 9.81 [3.99–24.13]; p < 0.001), and the presence of a central venous catheter (OR 5.02 [95% CI 1.84–13.67]; p = 0.002) as independently associated with an increased risk of VTE. (4) Conclusions: This prospective cohort study provides unprecedented evidence that cancer patients have no increased risk of developing VTE after the third dose of tozinameran, regardless of the type of active therapy. The specific pattern of lymphocyte response appears to increase thromboembolic risk, underlying immune dysregulation as a causal cofactor. These findings emphasize the need for additional monitoring after periodic COVID-19 vaccination in cancer patients. Full article

(1) Background: Allergic disorders and systemic lupus erythematosus (SLE) are immune dysregulation conditions that are increasingly prevalent, with growing evidence suggesting shared pathogenesis. (2) Results: Patients with SLE have a higher risk of allergic conditions, particularly allergic rhinitis and asthma; notably, children born to mothers with SLE show an increased asthma risk. This association appears linked to shared mechanisms involving T-helper 2 cells, IgE, human leukocyte antigen, genetic factors, and environmental triggers. Various medications used in allergic disorders and SLE have benefits in both diseases. Many SLE medications benefit allergic dermatitis. Meanwhile, omalizumab used for severe asthma may reduce SLE activity. (3) Conclusions: More research is essential to clarify the shared pathways and cross-benefits of treatments for allergic disorders and SLE. Novel treatment strategies are warranted to clarify the roles of biologic treatment in allergic disorders in the setting of SLE. Full article

Background: Lung adenocarcinoma (LUAD) is a common histopathological variant of non-small cell lung cancer. Individuals with type 2 diabetes (T2DM) face an elevated risk of developing LUAD. We examined the common genomic characteristics between LUAD and T2DM through bioinformatics analysis. Methods: We acquired the GSE40791, GSE25724, GSE10072, and GSE71416 datasets. Differentially expressed genes (DEGs) were identified through R software, particularly its version 4.1.3 and analyzed via gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Subsequently, we analyzed the relationship between immune cell infiltration and DEGs. we constructed a protein–protein interaction network using STRING and visualized it with Cytoscape. Moreover, gene modules were identified utilizing the MCODE plugin, and hub genes were selected through the CytoHubba plugin. Additionally, we evaluated the predictive significance of hub genes using receiver operating characteristic curves and identified the final central hub genes. Finally, we forecasted the regulatory networks of miRNA and transcription factors for the central hub genes. Results: A total of 748 DEGs were identified. Analysis of immune infiltration showed a notable accumulation of effector-memory CD8 T cells, T follicular helper cells, type 1 T helper cells, activated B cells, natural killer cells, macrophages, and neutrophils in both LUAD and T2DM. Moreover, these DEGs were predominantly enriched in immune-related pathways, including the positive regulation of I-κB kinase/NF-κB signaling, positive regulation of immunoglobulin production, cellular response to interleukin-7, and cellular response to interleukin-4. The TGF-β signaling pathway was significantly important among them. Additionally, seven hub genes were identified, including ATR, RFC4, MCM2, NUP155, NUP107, NUP85, and NUP37. Among them, ATR, RFC4, and MCM2 were identified as pivotal hub genes. Additionally, hsa-mir147a, hsa-mir16-5p, and hsa-mir-1-3p were associated with LUAD and T2DM. SP1 (specific protein 1) and KDM5A (lysine-specific demethylase 5A) regulated MCM2, ATR, and RFC4. Conclusions: Our study elucidates the common mechanisms of immune response, TGF-β signaling pathway, and natural killer cells in LUAD and T2DM, and identifies ATR, RFC4, and MCM2 as key potential biomarkers and therapeutic targets for the comorbidity of these two conditions. Full article

Recently, the “epithelial barrier hypothesis” has been proposed as a key factor in the development of allergic diseases, such as food allergies. Harmful environmental factors can damage epithelial barriers, with detrimental effects on the host immune response and on the local microbial equilibrium, resulting in chronic mucosal inflammation that perpetuates the dysfunction of the epithelial barrier. The increased epithelial permeability allows allergens to access the submucosae, leading to an imbalance between type 1 T-helper (Th1) and type 2 T-helper (Th2) inflammation, with a predominant Th2 response that is the key factor in food allergy development. In this article on the state of the art, we review scientific evidence on the “epithelial barrier hypothesis”, with a focus on food allergies. We describe how loss of integrity of the skin and intestinal epithelial barrier and modifications in gut microbiota composition can contribute to local inflammatory changes and immunological unbalance that can lead to the development of food allergies. Full article

Background/Objectives: Commercial poultry flocks undergo Salmonella vaccinations to manage salmonellosis outbreaks. Due to reports of severe injection site reactions to Salmonella bacterins, assessment of local inflammatory responses is necessary. The objective was to assess local inflammatory and systemic humoral immune responses to commercial autogenous Salmonella bacterin vaccines (SV1 or SV2) following primary or secondary intradermal (i.d.) vaccination in Light-Brown Leghorns (LBLs). Methods: LBL pullets received primary (14 wks) or secondary (19 wks) vaccination by i.d. growing feather (GF) pulp injection of SV1, SV2, Salmonella Enteritidis (SE) lipopolysaccharide (LPS), or water–oil–water emulsion (V). Local leukocyte levels and relative cytokine mRNA expression were monitored before (0 d) and at 6 h, 1 d, 2 d, 3 d, 5 d, and 7 d post-GF pulp injection (p.i.). Blood was collected through 28 d post-primary or -secondary vaccination, and SE-specific antibodies were quantified via ELISA. Results: Primary vaccine administration increased local heterophil and macrophage levels and increased IL-6 and IL-8 mRNA expressions at 6 h p.i., independent of treatment. Secondary administration extended these local immune activities through 3 d p.i. and included prolonged IL-17A mRNA expression. Primary and secondary GF-pulp injection with V resulted in rapid lymphocyte recruitment by 6 h p.i., comprised primarily of CD4⁺ and γδ T cells. SV1 and SV2 also produced a T-dependent systemic humoral immune response, as indicated by the IgM-to-IgG isotype switch, along with a memory phenotype in the secondary response. Conclusions: These commercial-killed Salmonella vaccines, when prepared in water–oil–water emulsions, stimulated prolonged innate and T helper (Th) 17-type inflammatory responses at the injection site and produced a classic systemic humoral immune response after a second vaccination. Further research is needed to determine if extended inflammation influences adaptive immune responses in eliminating Salmonella infection. Full article

Immunoglobulin E (IgE)-mediated food allergy has been dramatically increasing in incidence over the last few decades. The combinations of both genetic and environmental factors that affect the microbiome and immune system have demonstrated significant roles in its pathogenesis. The morbidity, and at times mortality, that occurs as the result of this specific, reproducible, but impaired immune response is due to the nature of the shift from a regulatory T (Treg) cellular response to a T helper 2 (Th2) cellular response. This imbalance caused by food allergens results in an interleukin (IL)-4 and IL-13 dominant environment that drives B cell activation and differentiation into IgE-producing plasma cells. The resulting symptoms can range from mild to more severe anaphylaxis, and even death. Current therapeutic strategies involve avoidance and broad symptom management upon accidental exposure; however, no definitive cure exists. This narrative review highlights how the elucidation of the pathogenesis of IgE-mediated food allergy resulted in the development of therapeutics that are more specific to these individual receptors and molecules which have been relatively successful in mitigating this potentially life-threatening allergic response. However, potential adverse effects and re-sensitization following the conclusion of treatment has urged the need for improved therapeutic methods. Therefore, given the understanding of their mechanism of action and the overlap with the mechanism of IgE-mediated food allergies, probiotics and small molecule natural compounds may provide novel therapeutic and preventative strategies. This is compelling, as they have demonstrated success in clinical trials and may provide hope to improve quality of life in allergy patients. Full article

Atopy is defined as a predisposition to hypersensitivity reactions against a range of antigens. It is characterized by the activation of CD4+ T helper type 2 (Th2) cells and an increased production of immunoglobulin E (IgE). The most common atopic conditions are atopic dermatitis, asthma, allergic rhinitis, food allergies, and atopic ocular diseases. Atopic keratoconjunctivitis (AKC) is a chronic, bilateral inflammatory condition affecting the ocular surface, frequently occurring in conjunction with atopic dermatitis. It is not uncommon for patients to present with multiple conditions simultaneously or in a sequential manner. A comprehensive understanding of the underlying mechanisms of atopic diseases is essential for the effective clinical evaluation and treatment. Recent research has underscored the pivotal role of the microbiota in the pathogenesis of atopic dermatitis and atopic eye diseases, with alterations in microbial composition (dysbiosis) being linked to a spectrum of atopic conditions. Probiotics are currently being investigated as a potential treatment option for restoring microbial balance and alleviating disease symptoms. This review examines the relationship between atopic dermatitis, atopic keratoconjunctivitis, and the microbiota, evaluating the current evidence and exploring the potential of probiotics as a novel therapeutic approach. Full article