Notch4 signaling limits regulatory T-cell-mediated tissue repair and promotes severe lung inflammation in viral infections.

A cardinal feature of COVID-19 is lung inflammation and respiratory failure. In a prospective multi-country cohort of COVID-19 patients, we found that increased Notch4 expression on circulating regulatory T (Treg) cells was associated with disease severity, predicted mortality, and declined upon recovery. Deletion of Notch4 in Treg cells or therapy with anti-Notch4 antibodies in conventional and humanized mice normalized the dysregulated innate immunity and rescued disease morbidity and mortality induced by a synthetic analog of viral RNA or by influenza H1N1 virus. Mechanistically, Notch4 suppressed the induction by interleukin-18 of amphiregulin, a cytokine necessary for tissue repair. Protection by Notch4 inhibition was recapitulated by therapy with Amphiregulin and, reciprocally, abrogated by its antagonism. Amphiregulin declined in COVID-19 subjects as a function of disease severity and Notch4 expression. Thus, Notch4 expression on Treg cells dynamically restrains amphiregulin-dependent tissue repair to promote severe lung inflammation, with therapeutic implications for COVID-19 and related infections.

Mistletoe (Viscum album L.) extract attenuates itraconazole-induced acute oxidative stress and hepatocellular injury in rats.

In the current study, the protective effect of a mistletoe extract (Helixor®, HLX) on Itraconazole (ITZ)-induced hepatocellular injury and acute oxidative stress in rats was aimed to be investigated by histological, biochemical and comet assay methods. Four groups a control group, an HLX group (5mg/kg/14days/intraperitoneally (ip)), an ITZ group (100mg/kg/14days/oral) and an HLX plus ITZ group (5mg/kg/14days/ip+100mg/kg/14days/oral) were all created from 32 female Wistar albino rats. At the end of the experiment, AST and ALT liver enzymes, total oxidant status (TOS) levels and total antioxidant status (TAS) levels, histopathological analysis and comet assay were carried out. Highest genotoxicity, higher levels of plasma AST and ALT, higher TOS, more degeneration of liver histopathology including hepatocyte degeneration, hepatocyte apoptosis and necrosis, portal/periportal inflammation, bile ductus hyperplasia and multinuclear giant cell formation were observed in ITZ group (p<0.05). As opposed to that, administration of HLX plus ITZ improved histopathological changes and DNA damage and showed a dramatic decrease in AST, ALT and TOS levels (p<0.05) and an increase in TAS level (p<0.001) when compared to ITZ group. This study showed that the antioxidant properties of HLX administration significantly decreased acute oxidative stress and hepatocellular damage in rats given ITZ.

Differential Expression of Novel Immune Checkpoint Receptors on Tumor Infiltrating Lymphocytes in Patients with Locally Advanced Breast Cancer after Neoadjuvant Chemotherapy.

Immune checkpoint receptors (ICRs) were recently found to modulate the anti-tumoral immune response. This study aimed to determine the clinical and pathological associations of ICRs expression on tumor-infiltrating lymphocytes (TILs) in patients with locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy (NAC). Expressions of ICRs including PD-1, LAG-3, TIM-3, TIGIT, and CTLA-4 on CD8+ T lymphocytes and Natural Killer (NK) cells on TILs were analyzed by flow cytometry. Patients <50 years were more likely to express CTLA-4 on CD8+ T lymphocytes compared to those ≥50 years (p=0.004). In addition, patients with ypT3-4 tumors were more likely to have increased LAG-3 expression on CD16-CD56bright NK cells (p=0.042) and PD-1 (p=0.014) and CTLA-4 (p=0.018) expressions on CD8+ T cells in regard to those with ypT1-T2, respectively. Contrarily, PD-1 expression on CD16-CD56bright NK cells was found to be decreased in patients with ypN+ compared to those with ypN- (p=0.022). Furthermore, patients with HER2+ tumors were more likely to have increased TIM-3 expression on CD8+ T cells (p=0.043), whereas patients with a better response to NAC were more likely to express TIGIT on CD8+ T (p=0.014) and CD16-CD56bright NK cells (p=0.003), respectively. The new generation ICRs, TIM-3, LAG-3, and TIGIT are highly expressed in LABC following NAC in patients with poor prognostic factors. Therefore, new evolving therapies using inhibitory mAbs directed to TIM-3, LAG-3, and TIGIT could be also be considered in locally advanced breast cancers expressing these ICRs.

The role of component-resolved diagnosis in Hymenoptera venom allergy in clinical practice.

Background: Hymenoptera venom allergy is an immunoglobulin (Ig) E mediated hypersensitivity reaction to Hymenoptera venoms. Obvious identification of the culprit insect that causes the clinical symptoms and, hence, the accurate selection of venom for curative treatment, is of great importance for the effectiveness and safety of venom immunotherapy. Objective: In this study, the contribution of component-resolved diagnostics (CRD) is evaluated in the diagnosis of Hymenoptera venom allergy. Method: Ninety-three patients from four different centers in Turkey were included in the study. Conventional tests, including prick and intradermal skin tests, with commercial venom extracts and serum specific IgE (sIgE) levels for whole venoms were performed. An sIgE analysis for venom allergen components, including rApi m 1, rApi m 2, rApi m 10, rVes v 1, rVes v 5, were evaluated by immunoblotting. Results: In conventional test results, 17 of 35 patients with bee venom allergy were positive to honey bee venom, whereas 18 patients were positive to bee and wasp venoms. In 28 of 35 patients with bee venom allergy, the diagnosis was confirmed with CRD. CRD revealed a sensitivity of 80% in patients with bee venom allergy. According to conventional tests, 7 of 24 patients with vespid venom allergy demonstrated sensitivity only to Vespula species, whereas 17 patients revealed double positivity. The total diagnostic sensitivity of Ves v 1 and Ves v 5 was calculated as 87.5%. Ten of 23 patients with a history of hypersensitivity to both venoms showed double sensitivity with CRD; one patient had cross-reactivity, one patient was found to be sensitive only to bee venom, and, eight patients were sensitive only to Vespula species. Eleven patients had an uncertain history in terms of the culprit insect type and six of them had double sensitivity in CRD. Conclusion: CRD seemed to be more helpful in diagnosing vespid venom allergy than bee venom allergy. It can also discriminate clinically significant sensitizations from irrelevant ones.

Selenium potentiates the anticancer effect of cisplatin against oxidative stress and calcium ion signaling-induced intracellular toxicity in MCF-7 breast cancer cells: involvement of the TRPV1 channel.

BACKGROUND: In breast cancers, calcium signaling is a main cause of proliferation and apoptosis of breast cancer cells. Although previous studies have implicated the transient receptor potential vanilloid 1 (TRPV1) cation channel, the synergistic inhibition effects of selenium (Se) and cisplatin in cancer and the suppression of ongoing apoptosis have not yet been investigated in MCF-7 breast cancer cells. This study investigates the anticancer properties of Se through TRPV1 channel activity in MCF-7 breast cancer cell line cultures when given alone or in combination with cisplatin. MATERIALS: The MCF-7 cells were divided into four groups: the control group, the Se-treated group (200 nM), the cisplatin-treated group (40 µM) and the Se + cisplatin-treated group. RESULTS: The intracellular free calcium ion concentration and current densities increased with TRPV1 channel activator capsaicin (0.01 mM), but they decreased with the TRPV1 blocker capsazepine (0.1 mM), Se, cisplatin, and Se + cisplatin incubations. However, mitochondrial membrane depolarization, apoptosis, and the caspase 3, and caspase 9 values increased in the Se-treated group and the cisplatin-treated group, although Western blot (procaspase 3 and 9) results and the cell viability levels decreased with the Se and Se + cisplatin treatments. Apoptosis and caspase-3 were further increased with the Se + cisplatin treatment. Intracellular reactive oxygen species production increased with the cisplatin treatment, but not with the Se treatment. CONCLUSION: This study's results report, for the first time, that at a cellular level, Se and cisplatin interact on the same intracellular toxic cascade, and the combination of these two drugs can result in a remarkable anticancer effect through modulation of the TRPV1.

Natural Killer Cell Subsets and Their Functional Activity in Behçet's Disease.

BACKGROUND: Behçet's disease (BD) is a rare, chronic autoinflammatory disorder of unknown origin. Natural killer (NK) cells are one of the major immunoregulatory cell groups of the innate immune system, but their role in BD pathogenesis is not well documented. OBJECTIVES: We aimed to investigate the role of NK cell subsets and their cytokine secretion and cytotoxic activity in patients with BD. PATIENTS AND METHODS: The study group consisted of BD patients who had only mucocutaneous involvement, and they were compared with healthy subjects. BD patients were divided into two groups according to their frequencies of oral ulcerations. NK cell cytotoxicity was determined using CD107a expression and a CFSE-based cytotoxicity test. Expression of NK cell receptors and surface markers and the intracellular IL-5, IL-10, IL-17, and IFN-γ levels in CD16+ NK cells were assessed by flow cytometry. RESULTS: Although the cytokine secretion pattern was different, no difference was obtained in cytotoxic activity, expression of activatory receptors, or degranulation of NK cells. CONCLUSION: Increases in NK1/NK2 ratio and CD16+IFN-γ+ NK1 cells might support the idea of a biased IFN-γ dominant immune response in the mucocutaneous involvement of BD pathogenesis. Although the cytokine secretion pattern was different, no difference was obtained in cytotoxic activity, expression of activatory receptors, or degranulation of NK cells.

Peripheral blood NK cells expressing HLA-G, IL-10 and TGF-ß in healthy donors and breast cancer patients.

Human natural killer (NK) cells are not only professional cytotoxic cells integrated into effector branch of innate immunity, but they are also regulatory cells, managing different immune processes. Immunoregulatory NK cells, expressing HLA-G and IL-10, have been generated in vitro from human hematopoietic progenitors and found in vivo among decidual NK cells of pregnant women. Human peripheral blood NK cells have been shown to acquire suppressive properties after HLA-G uptake during trogocytosis. Moreover, it has been shown that circulating NK cells contain a trace amount of cells producing TGF-ß and IL-10, which exert a suppressive influence upon innate and adaptive immunity. In this study, we report on a minor subset of peripheral blood HLA-G(+) NK cells possessing suppressive activity toward effector functions of NK cells. Further we demonstrate an increased number of circulating HLA-G(+), IL-10(+), and TGF-ß(+) NK cells in breast cancer patients which might impair efficiency of anti-tumor immunity.

Natural killer cells dominate a Th-1 polarized response in Behçet's disease patients with uveitis.

OBJECTIVES: Behçet's disease (BD) is a systemic inflammatory disorder of unknown etiology, characterised by recurring relapses and remissions. BD manifestations have been thought to be associated with the immunological abnormalities triggered by environmental factors in genetically susceptible individuals. Natural killer (NK) cells are important members of innate immunity with their cytotoxic activity and also cytokine secretions. They have the capacity to induce or dampen immune responses. Different study groups have reported conflicting results about NK cell activity in the BD pathogenesis, however, contribution of NK cells to BD is still unclear. METHODS: NK cells from BD patients with uveitis (n=11) as well as age- and gender-matched healthy controls (n=9) were purified and intracytoplasmic cytokine levels of TNF-α, IFN-γ, IL-2, IL-4, IL-10, IL-12 and IL-13 were determined. RESULTS: Increased TNF-α, IFN-γ and IL-2 in relapse period and increased IL-4 as well as a slight increase of IL-10 in remission period were observed. CONCLUSIONS: Our results show that NK cells are the contributors of BD pathogenesis with their NK1 profile in relapse periods, and also with their NK2 profile in remission periods, in BD patients with uveitis. An increase in IL-10 observed in remission periods may be linked to the regulatory potential of NK cells in the recurrent nature of BD manifestations.

Genetic variants of synaptic vesicle and presynaptic plasma membrane proteins in idiopathic generalized epilepsy.

BACKGROUND: The aim of this study was to analyze the role of the genetic variants of two synaptic vesicle proteins (VAMP2 and Synaptotagmin XI) and two presynaptic plasma membrane proteins (Syntaxin 1A and SNAP-25) in patients with idiopathic generalized epilepsy (IGE). METHOD: Eighty-five patients with IGE and 93 healthy subjects were included in the study. We analyzed the functional polymorphisms of VAMP2, Synaptotagmin XI, Syntaxin 1A and SNAP-25 genes with polymerase chain reaction and restriction fragment length polymorphism methods. RESULTS: In the patients with IGE, significant differences alleles and genotypes of 26 bp Ins/Del polymorphism of the VAMP2 gene and the 33-bp promoter region of Synaptotagmin XI were observed, however no associaton was found regarding Intron 7 rs1569061 of Syntaxin 1A gene, MnlI rs3746544 and DdeI rs1051312 polymorphisms of SNAP-25 gene compared with healthy subjects. Carriers of the C allele of Synaptotagmin XI had worse measures compared with the T allele of Synaptotagmin XI. In the haplotype analysis, the frequency of the T alleles of rs1569061 and of the C alleles of the 33-bp promoter region of Synaptotagmin XI was found to be significantly higher in patients with IGE as compared with the healthy subjects. CONCLUSION: The genetic variations of VAMP2, Synaptotagmin XI might be indication of the relationship between these genes and IGE.

A stimulatory role of ozone exposure on human natural killer cells.

Ozone is claimed to have beneficial effects. While studies revealed the safe therapeutic use of ozone, there are conflicting results for the link between immune system and ozone encounter. Natural killer (NK) cells are important sentinels of immunity with their cytotoxic activity and immune-regulatory potentials. This study aimed to investigate the effects of direct ozone encountering on human immune system, at cellular level. Survival, proliferative capacity and subset content of peripheral blood mononuclear cells (PBMC) were analysed. PBMC of healthy donors (n=5, mean age: 27±6 years) were exposed to 1, 5, 10 and 50 µg/mL doses of medical ozone, directly injected into culture wells, once, initially. 1 and 5 µg/mL doses didn't show toxic effects while 10 and 50 µg/mL doses were toxic. PBMC were cultured for 5 days following 1 and 5 µg/mL ozone encountering. 1 µg/mL dose increased numbers of CD3-CD16+/56+ NK cells among PBMC. Following stimulation with ozone, no difference was observed in basal and phytohemaglutinin-stimulated proliferative capacity. 1 and 5 µg/mL doses of ozone were found to increase NK cytotoxicity. These data indicates influential effects of transient ozone exposure on NK cells, which in turn may have a role in control of immune responses.

IL-22-secreting Th22 and IFN-γ-secreting Th17 cells in Behçet's disease.

OBJECTIVE: Behçet's disease (BD) is a systemic inflammatory disease with unknown etiology. Studies have shown that some T helper (Th) 1-associated cytokines have role in the inflammation of BD. The CD4(+) Th cells can be differentiated into Th1, Th2, Th17 and Th22 secrete different cytokines to regulate immune system. In this study, cytokine secretion of Th subsets in BD was investigated. METHODS: The study group consisted of 26 BD patients with mucocutaneous involvement and 12 healthy subjects. Lymphocyte subpopulations, IL-5, IL-10, IL-17, IL-22 and IFN-γ secretion of CD4(+) T and Foxp3(+) Treg cells were determined by flow cytometry. RESULTS: Compared with healthy subjects, Th1 (IL-17A(-)IL-22(-)IFN-γ(+)), Th22 (IL-17A(-)IL-22(+)IFN-γ) and IL-17A(+)IFN-γ(+)-secreting cells were significantly increased, and the percentage of Treg cells were dramatically reduced in BD patients. The frequency of recurrent oral ulcers was associated with increased Th22 cells. CONCLUSIONS: Our study describes an association between Th22 cell subset and IL-17A(+) IFNγ(+)-secreting cells with mucocutaneous BD. These findings revealed that reduced levels of Tregs and increased levels of Th1 and Th22 cells as well as Th17/Th1 cells might be associated with the pathogenesis of BD.

In Vitro Synergistic Photodynamic, Photothermal, Chemodynamic, and Starvation Therapy Performance of Chlorin e6 Immobilized, Polydopamine-Coated Hollow, Porous Ceria-Based, Hypoxia-Tolerant Nanozymes Carrying a Cascade System.

A synergistic therapy agent (STA) with photothermal, photodynamic, chemodynamic, and starvation therapy (PTT, PDT, CDT, and ST) functions was developed. Hollow, mesoporous, and nearly uniform CeO2 nanoparticles (H-CeO2 NPs) were synthesized using a staged shape templating sol-gel protocol. Chlorin e6 (Ce6) was adsorbed onto H-CeO2 NPs, and a thin polydopamine (PDA) layer was formed on Ce6-adsorbed H-CeO2 NPs. Glucose oxidase (GOx) was bound onto PDA-coated Ce6-adsorbed H-CeO2 NPs to obtain the targeted STA (H-CeO2@Ce6@PDA@GOx NPs). A reversible photothermal conversion behavior with the temperature elevations up to 34 °C was observed by NIR laser irradiation at 808 nm. A cascade enzyme system based on immobilized GOx and intrinsic catalase-like activity of H-CeO2 NPs was rendered on STA for enhancing the effectiveness of PDT by elevation of ROS generation and alleviation of hypoxia in a tumor microenvironment. Glucose-mediated generation of highly toxic hydroxyl radicals (·OH) was evaluated for CDT. The effectiveness of PDT on glioblastoma T98G cells was markedly enhanced by O2 generation started by the decomposition of glucose. A similar increase in cell death was also observed when ST and CDT functions were enhanced by photothermal action. The viability of T98G cells decreased to 10.6% by in vitro synergistic action including ST, CDT, PDT, and PTT without using any antitumor agent.

Stem cell treatment reduces T cell apoptosis in COPD patients with chronic bronchitis but not with emphysema.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a prevalent and preventable condition. Mesenchymal stem cell (MSC) therapy is being explored to aid in the regeneration of lung cells and airway structure, aiming to restore lung function. AIM: To examine varied responses of MSCs when cultured with peripheral blood mononuclear cells (PBMCs) from different COPD phenotypes, patients were grouped into ACOS, emphysema, and chronic bronchitis categories. METHODS: PBMCs from these groups and controls were co-cultured with MSCs derived from dental follicles, revealing differing rates of apoptosis among COPD phenotypes compared to controls. RESULTS: While the chronic bronchitis group exhibited the least lymphocyte viability (p<0.01), introducing MSCs notably enhanced viability across all phenotypes except emphysema, with the chronic bronchitis group showing the most improvement (p<0.05). CONCLUSION: Stem cell therapy might reduce peripheral lymphocyte apoptosis in COPD, with varying responses based on phenotype, necessitating further research to understand mechanisms and optimize tailored therapies for each COPD subtype.

Behçet's disease: immunological relevance with arthritis of ankylosing spondylitis.

Behçet's disease (BD) is a multi-system inflammatory disorder, in which cytokine balance is polarized to Th1. In this study, the cell surface molecule expression, Th1/Th2, inflammatory cytokine levels in blood, and synovial fluid of CD3(+) T lymphocytes in BD were investigated. The study group consisted of 10 BD, 10 ankylosing spondylitis (AS) patients with peripheral arthritis, and 10 healthy subjects. Expression of cell surface molecules, intracellular IL-2, IL-5, IL-8, IL-10, IL-12, IFN-γ, and TNF-α levels in CD3(+) T lymphocytes were determined by flow cytometry in synovial and peripheral blood mononuclear cells (PBMCs). Synovial and plasma cytokine levels were measured by ELISA and CBA. In PBMCs, CD4, CD25, HLA-DR expression and intracellular IL-12, and TNF-α levels of CD3(+) T lymphocytes were statistically increased in BD patients compared to healthy subjects. Compare to AS patients, CD25 and HLA-DR surface expression and intracellular IFN-γ and TNF-α levels in T cells were significantly elevated in BD patients. In BD patients, there was an increase in IL-8 secretion; however, in AS patients, both Th1- and Th2-type cytokines were increased compare to healthy subjects. Intracellular cytokine expression did not show any difference in BD patients; however, IL-12 content of synovial fluid was significantly increased compared to AS patients. Our findings revealed that Th1 polarization occurred in both peripheral blood and synovial fluid of BD patients with arthritis. It is found no difference between synovial fluid analysis of BD and AS patients, showing the similarities in the pathogenesis of both diseases.

Investigation of UV-treated mesenchymal stem cells in an in vitro wound model.

This study examines the effects of ultraviolet-induced adipose tissue-derived mesenchymal stem cells and their supernatants on wound healing regarding cell viability, percentage of wound healing, released cytokine, and growth factors. It has been reported in previous studies that mesenchymal stem cells are resistant to ultraviolet light and have a protective effect on skin cells against ultraviolet-induced damage. At the same time, there are many studies in the literature about the positive effects of cytokines and growth factors secreted by mesenchymal stem cells. Based on this information, the effects of ultraviolet-induced adipose-derived stem cells and supernatants containing their secreted cytokines and growth factors on an in vitro two-dimensional wound model created with two different cell lines were investigated in this study. It was determined from the results that the highest cell viability and the least apoptotic staining were 100 mJ in mesenchymal stem cells (**p < 0.01). Furthermore, analysis of cytokines and growth factors collected from supernatants also supported 100 mJ as the optimal ultraviolet dose. It was observed that cells treated with ultraviolet and their supernatants significantly increased cell viability and wound-healing rate over time compared to other groups. In conclusion, with this study, it has been shown that adipose-derived stem cells exposed to ultraviolet light can have an important use in wound healing, both with their potential and with the more cytokines and growth factors they secrete. However, further analysis and animal experiments should be performed before clinical use.

Synthesis, Structural Investigations, DNA/BSA Interactions, Molecular Docking Studies, and Anticancer Activity of a New 1,4-Disubstituted 1,2,3-Triazole Derivative.

We report herein a new 1,2,3-triazole derivative, namely, 4-((1-(3,4-dichlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)-2-hydroxybenzaldehyde, which was synthesized by copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The structure of the compound was analyzed using Fourier transform infrared spectroscopy (FTIR), 1H NMR, 13C NMR, UV-vis, and elemental analyses. Moreover, X-ray crystallography studies demonstrated that the compound adapted a monoclinic crystal system with the P21/c space group. The dominant interactions formed in the crystal packing were found to be hydrogen bonding and van der Waals interactions according to Hirshfeld surface (HS) analysis. The volume of the crystal voids and the percentage of free spaces in the unit cell were calculated as 152.10 Å3 and 9.80%, respectively. The evaluation of energy frameworks showed that stabilization of the compound was dominated by dispersion energy contributions. Both in vitro and in silico investigations on the DNA/bovine serum albumin (BSA) binding activity of the compound showed that the CT-DNA binding activity of the compound was mediated via intercalation and BSA binding activity was mediated via both polar and hydrophobic interactions. The anticancer activity of the compound was also tested by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using human cell lines including MDA-MB-231, LNCaP, Caco-2, and HEK-293. The compound exhibited more cytotoxic activity than cisplatin and etoposide on Caco-2 cancer cell lines with an IC50 value of 16.63 ± 0.27 µM after 48 h. Annexin V suggests the induction of cell death by apoptosis. Compound 3 significantly increased the loss of mitochondrial membrane potential (MMP) levels in Caco-2 cells, and the reactive oxygen species (ROS) assay proved that compound 3 could induce apoptosis by ROS generation.

The Notch1/CD22 signaling axis disrupts Treg function in SARS-CoV-2-associated multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) evolves in some pediatric patients following acute infection with SARS-CoV-2 by hitherto unknown mechanisms. Whereas acute-COVID-19 severity and outcomes were previously correlated with Notch4 expression on Tregs, here, we show that Tregs in MIS-C were destabilized through a Notch1-dependent mechanism. Genetic analysis revealed that patients with MIS-C had enrichment of rare deleterious variants affecting inflammation and autoimmunity pathways, including dominant-negative mutations in the Notch1 regulators NUMB and NUMBL leading to Notch1 upregulation. Notch1 signaling in Tregs induced CD22, leading to their destabilization in a mTORC1-dependent manner and to the promotion of systemic inflammation. These results identify a Notch1/CD22 signaling axis that disrupts Treg function in MIS-C and point to distinct immune checkpoints controlled by individual Treg Notch receptors that shape the inflammatory outcome in SARS-CoV-2 infection.

The decreased CD4+CD25+ FoxP3+ T cells in nonstimulated allergic rhinitis patients sensitized to house dust mites.

OBJECTIVE: Regulatory (CD4(+)CD25(+)) T cells have been shown to play an important role in the development of allergic diseases. This study aims to investigate CD4(+)CD25(+) T cells, Forkhead box P3 (FoxP3(+) cells), and T-helper 1/T-helper 2 (Th1/Th2) cytokines in newly diagnosed allergic rhinitis (AR) patients. METHODS: Altogether, 10 subjects with AR and 12 age-matched nonallergic healthy subjects were included in this study. CD4(+)CD25(+) T cells, FoxP3(+) T cells in peripheral blood mononuclear cells (PBMCs) were evaluated by flow cytometry, and the Th1/Th2 cytokine levels were determined by cytometric bead array immunoassay in both PBMC supernatants and nasal lavage fluids. RESULTS: The percentage of CD4(+)CD25(+) T cells were significantly higher, whereas the percentage of FoxP3(+) cells were lower in AR patients compared with healthy subjects. In PBMC culture supernatants, interleukin-10 (IL-10) levels were significantly lower (p = .012), whereas IL-4, IL-5, and tumor necrosis factor-α (TNF-α) levels in nasal lavage fluids were higher in AR patients compared with healthy subjects (p = .026, p = .015, p = .03, respectively). CONCLUSIONS: Our findings indicate that decrease in CD4(+)CD25(+)FoxP3(+) T cell fraction and diminished levels of IL-10 are noteworthy without allergen stimulation in house dust mite AR patients.