scholarly journals Features of cytokine signaling forming T-helper immune response in COPD of varying severity

2020 ◽  
Vol 9 (2) ◽  
Author(s):  
Tatyana I. Vitkina ◽  
Karolina A. Sidletskaya
Keyword(s):  
Immune Response ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Cytokine Profile ◽  
Cytokine Signaling ◽  
Control Group ◽  
T Helper ◽  
Th Cells ◽  
Copd Patients ◽  
Severe Copd

Introduction — Currently, chronic obstructive pulmonary disease (COPD) is a global public health problem. However, molecular mechanisms of the development of this pathology are still poorly understood. The aim is to establish mechanisms of cytokine regulation of T-helper (Th) immune pathway in patients with COPD of varying severity. Material and Methods — The study included 112 patients with stable COPD (mild, moderate and severe grade) and 32 healthy volunteers (control group). We investigated serum cytokine levels (tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin 4 (IL-4), IL-6, IL-10, IL-17A) and the percentage of circulating Th cells (CD4+) expressing membrane receptor to IL-6 (IL-6R or CD126+), using flow cytometry. The levels of transforming growth factor-β1 (TGF-β1) and IL-21 were detected by ELISA. The direction of immune response in COPD patients was determined depending on the prevalence of cytokines playing a crucial role in the formation of certain Th cells type (Th1, Th17). Results — Th1-associated cytokine profile was expressed at the initial stage of COPD; the Th17-associated cytokine profile begins to prevail at severe COPD. Among COPD patients with Th1-associated cytokine profile, a statistically significant increase in the number of CD4+CD126+ cells in comparison with the control group was identified only in severe COPD. In the group of COPD patients with Th17-associated cytokine profile, an increase in the number of CD4+CD126+ cells were observed at all severity stages of the pathology. Conclusion — Moderate and severe COPD are characterized by the predominance of Th17-associated cytokine profile leading to chronic inflammation. The increase in IL-6R expression levels in circulating CD4+ cells serves as the mechanism for enhancing Th17-associated response in COPD.

scholarly journals Impact of Low-Dose Occupational Exposure to Ionizing Radiation on T-Cell Populations and Subpopulations and Humoral Factors Included in the Immune Response

Dose-Response ◽  
2018 ◽  
Vol 16 (3) ◽  
pp. 155932581878556 ◽  
Author(s):  
Ilona Gyuleva ◽  
Jana Djounova ◽  
Ivanka Rupova
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Occupational Exposure ◽  
Low Dose ◽  
Dose Range ◽  
Interleukin 2 ◽  
Cell Populations ◽  
Control Group ◽  
T Helper ◽  
Humoral Factors

The aim of the present study is to assess the effects of low-dose occupational exposure on T helper response. One Hundred five employees working in Nuclear Power Plant, Kozloduy, Bulgaria and control group of 32 persons are included in this investigation. Flow cytometry measurements of T-cell populations and subpopulations and natural killer T cells are performed and levels of G, A, and M immunoglobulins and interleukin 2 (IL-2), IL-4, and interferon γ were determined. The data interpreted with regard to cumulative doses, length of service, and age. The results of the present study are not enough to outline a clear impact of occupational radiation exposure on T helper populations. Nevertheless, the observed even slight trends in some lymphocyte’s populations and in cytokines profile give us the reason to assume a possibility of a gradual polarization of T helper 1 to T helper 2 immune response at dose range 100 to 200 mSv. The results of the present study indicate the need to perform a more detailed epidemiological survey including potential confounding and misclassifying factors and possible selection bias that could influence the results.

scholarly journals Loss of SOCS3 in T helper cells resulted in reduced immune responses and hyperproduction of interleukin 10 and transforming growth factor–β1

2006 ◽  
Vol 203 (4) ◽  
pp. 1021-1031 ◽  
Author(s):  
Ichiko Kinjyo ◽  
Hiromasa Inoue ◽  
Shinjiro Hamano ◽  
Satoru Fukuyama ◽  
Takeru Yoshimura ◽  
...  
Keyword(s):  
T Cells ◽  
Growth Factor ◽  
Immune Responses ◽  
Leishmania Major ◽  
Transforming Growth Factor ◽  
Dominant Negative ◽  
Conditional Knockout ◽  
Cytokine Signaling ◽  
T Helper ◽  
Tgf Β1

Suppressor of cytokine signaling (SOCS)3 is a major negative feedback regulator of signal transducer and activator of transcription (STAT)3-activating cytokines. Transgenic mouse studies indicate that high levels of SOCS3 in T cells result in type 2 T helper cell (Th2) skewing and lead to hypersensitivity to allergic diseases. To define the physiological roles of SOCS3 in T cells, we generated T cell–specific SOCS3 conditional knockout mice. We found that the mice lacking SOCS3 in T cells showed reduced immune responses not only to ovalbumin-induced airway hyperresponsiveness but also to Leishmania major infection. In vitro, SOCS3-deficient CD4+ T cells produced more transforming growth factor (TGF)-β1 and interleukin (IL)-10, but less IL-4 than control T cells, suggesting preferential Th3-like differentiation. We found that STAT3 positively regulates TGF-β1 promoter activity depending on the potential STAT3 binding sites. Furthermore, chromatin immunoprecipitation assay revealed that more STAT3 was recruited to the TGF-β1 promoter in SOCS3-deficient T cells than in control T cells. The activated STAT3 enhanced TGF-β1 and IL-10 expression in T cells, whereas the dominant-negative form of STAT3 suppressed these. From these findings, we propose that SOCS3 regulates the production of the immunoregulatory cytokines TGF-β1 and IL-10 through modulating STAT3 activation.

scholarly journals Analysis of the frequency of single nucleotide polymorphisms in cytokine genes in patients with New Onset Diabetes After Transplant

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mohamed Jahromi ◽  
Torki Al-Otaibi ◽  
Osama Ashry Gheith ◽  
Nashwa Farouk Othman ◽  
Tarek Mahmoud ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Transforming Growth Factor ◽  
Interferon Γ ◽  
Cytokine Profile ◽  
Control Group ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Onset Diabetes ◽  
Metabolic Complication ◽  
New Onset

AbstractNew Onset Diabetes After Transplantation (NODAT) is a serious metabolic complication. While β-cell dysfunction is considered the main contributing factor in the development of NODAT, the precise pathogenesis is not well understood. Cytokines are thought to be involved in the inflammation of islet β-cells in diabetes; however, few studies have investigated this hypothesis in NODAT. A total of 309 kidney transplant recipients (KTRs) were included in this study. An association between kidney transplants, and the development of diabetes after transplant (NODAT) was investigated. Comparison was made between KTRs who develop diabetes (NODAT cases) or did not develop diabetes (control), using key cytokines, IL-6 G (− 174)C, macrophage mediator; IL-4 C (− 490)T, T helper (Th)-2 cytokine profile initiator; Th-1 cytokine profile initiator interferon-γ T (+ 874) A gene and TGF β1 C (+ 869) T gene polymorphisms were investigated. The genes were amplified using well-established polymerase chain reaction (PCR) techniques in our laboratory. Compared to the AA and AT genotypes of interferon gamma (IFNG), there was a strong association between the TT genotype of IFNG and NODAT kidney transplant recipients (KTRs) versus non-NODAT KTRs (p = 0.005). The AA genotype of IFNG was found to be predominant in the control group (p = 0.004). Also, significant variations of IL6 G (− 174) C, IL-4 C (− 590) T, interferon-γ T (+ 874) A gene and transforming growth factor β1 C (+ 869) T may contribute to NODAT. Our data is consistent with theTh-1/T-reg pathway of immunity. Further larger pan Arab studies are required to confirm our findings.

scholarly journals Altered peripheral blood Th17 and follicular T-helper subsets in patients with pulmonary tuberculosis

2019 ◽  
Vol 9 (2) ◽  
pp. 304-314
Author(s):  
I. V. Kudryavtsev ◽  
M. K Serebriakova ◽  
A. A. Starshinova ◽  
Yu. S. Zinchenko ◽  
N. Yu. Basantsova ◽  
...  
Keyword(s):  
T Cell ◽  
Peripheral Blood ◽  
Central Memory ◽  
T Cell Subsets ◽  
Th2 Cells ◽  
Effector Memory ◽  
Control Group ◽  
T Helper ◽  
Th Cells ◽  
Tfh Cells

Tuberculosis (TB) is one of the most common infections worldwide. Eradication of an intracellular pathogen M. tuberculosis requires to induce a Th1 response by activating IFNγ-producing tissue macrophages. Along with Th1 cells, various subsets of Th17 and follicular T-helper cells (Tfh) able to secrete a broad range of cytokines, including IFNγ, can also be involved in eliminating bacterial pathogens. It justified analyzing in this study changes in percentage of various peripheral blood Th subsets, including Th1, Th2, Th17 and Tfh cells, in TB patients. For this, major CD3+CD4+T cell subsets were assessed by using multicolor flow cytometry in TB patients (n = 40) and healthy volunteers (n = 30). It was found that in TB patients vs. control group percentage of peripheral blood CD45RA–CCR7+ central memory (CM) Th was decreased also affecting frequency of some functional T cell subsets, e.g. either lowering Th2 cells (9.11% (6.95; 13.77) vs. 7.21% (5.64; 9.84), p = 0.012) or elevating CCR6+ Th17 subsets (35.92% (27.72; 41.06) vs. 40.39% (35.41; 47.79; p = 0.016), respectively, but not influencing Th1 and Tfh subsets frequencies. Moreover, percentage of total CCR6+CM Th cells in TB patients vs. control was decreased in CCR4–CXCR3+Th17.1 cell subset (42.87% (33.64; 49.45) vs. 52.26% (46.45; 56.95), p < 0.001), whereas standard CCR4+CXCR3–Th17 and CCR6+ DP Th17 subsets were elevated (p = 0.005 and p = 0.002, respectively). In addition, altered Tfh subset composition associated with the increased (p = 0.021) percentage of CXCR3–CCR6–Tfh2 cells, but decreased CXCR3+CCR6–Tfh1 cells (p = 0.036) was observed. Finally, frequency of peripheral blood Th subsets noted above was also analyzed within effector memory (CD45RA–CCR7–) cells. It was found that in TB patients vs. volunteers frequency of Th17.1 cells was also significantly lower (p = 0.006) in CCR6+EM Th (54.43% (41.19; 91.92) vs. 61.76% (54.01; 65.63), whereas percentage of double-positive Th17 was significantly increased (20.83% (15.12; 30.87) and 12.93 % (9.80; 19.01), respectively, p < 0.001). Thus, it suggests that during M. tuberculosis infection percentage of IFNγ-producing Th17 and Tfh cells was reduced compared to control group also affecting both central memory Th cells patrolling peripheral lymphoid organs as well as effector memory Th cells able to exit to site of infection. 

Intranodal injection of semimature monocyte-derived dendritic cells induces T helper type 1 responses to protein neoantigen

Blood ◽  
2003 ◽  
Vol 102 (1) ◽  
pp. 36-42 ◽  
Author(s):  
Michel Gilliet ◽  
Martin Kleinhans ◽  
Erica Lantelme ◽  
Dirk Schadendorf ◽  
Günter Burg ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Cytokine Profile ◽  
Cd4 T Cell ◽  
Delayed Type Hypersensitivity ◽  
T Helper

Abstract Dendritic cells (DCs) represent the most potent antigen-presenting cells of the immune system capable of initiating primary immune responses to neoantigens. Here we characterize the primary CD4 T-cell immune response to protein keyhole limpet hemocyanin (KLH) in 5 metastatic melanoma patients undergoing a tumor peptide–based dendritic cell vaccination trial. Monocyte-derived dendritic cells displaying a semimature phenotype, as defined by surface markers, were loaded ex vivo with antigen and injected intranodally at weekly intervals for 4 weeks. All patients developed a strong and long-lasting delayed-type hypersensitivity reactivity to KLH, which correlated with the induction of KLH-dependent proliferation of CD4 T cells in vitro. Secondary in vitro stimulation with KLH showed significant increase in interferon-γ and interleukin-2 (IL-2) but not IL-4, IL-5, nor IL-10 secretion by bulk T cells. On the single-cell level, most TH1 cells among in vitro–generated KLH-specific T-cell lines confirmed the preferential induction of a KLH-specific type 1 T helper immune response. Furthermore, the induction of KLH-specific antibodies of the IgG2 subtype may reflect the induction of a type 1 cytokine profile in vivo after vaccination. Our results indicate that intranodal vaccination with semimature DCs can prime strong, long-lasting CD4 T-cell responses with a TH1-type cytokine profile in cancer patients. (Blood. 2003;102:36-42)

scholarly journals CLINICAL AND IMMUNOLOGICAL COMPARISONS IN Th- DEPENDENT IMMUNE RESPONSE MECHANISMS AMONG PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE

2018 ◽  
Vol 20 (6) ◽  
pp. 855-864 ◽  
Author(s):  
E. P. Kalinina ◽  
T. I. Vitkina ◽  
V. V. Knyshova ◽  
E. A. Fedoseeva ◽  
T. P. Novgorodtseva ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Immune Response ◽  
T Lymphocytes ◽  
T Helper Cells ◽  
Chronic Obstructive ◽  
Dependent Types ◽  
T Helper ◽  
Obstructive Pulmonary Disease ◽  
Moderate Severity ◽  
Copd Patients

Chronic obstructive pulmonary disease (COPD) is a global public health problem. Studies in immunological features and their correlations with clinical course of COPD are of importance. The aim of this study was to elucidate clinical and immunological features in COPD of different severity grade, concerning Th1- and Тh17-dependent types of immune response.The study included 132 COPD patients and 32 healthy individuals. According to clinical and functional patterns, the patients with COPD were divided into 3 groups, i.e., 36 cases (28%) of mild severity; 62 individuals (48%), of moderate severity, and 30 patients (23%) of severe clinical grade. We have performed both clinical and immunological evaluation of the patients. The Th1- and Th17-specific lymphocyte subpopulations were assessed according to the serum levels of cytokines, i.e. tumor necrosis factor (TNFα), IL-4, IL-10, IL-17A, IL-21, IFNγ, as well as transforming growth factor β1 (TGF-β1). We have also determined expression of IL-6R receptor (CD126+) on mature T lymphocytes (CD3+) and T helper cells (CD4+) from peripheral blood. We have obtained the following results: the patients with mild-grade COPD exhibited three different T cell phenotypes were determined, with a prevalence of Th1-dependent immune response. The IL-6R were mostly expressed on CD3+CD126+ cells for the Th1/Th17 phenotype, and CD4+CD126+ cells in cases of Th17-dependent type immune response. In patients with COPD of moderate severity, the Th1, Th17, or Th1/Th17 types of immune response was revealed at similar rates. The level of IL-6R expression on mature T lymphocytes and T-helper cells increased to the greatest extent in cases of Th17-dependent immune response. In severe COPD patients, we have found a dominance of Th17 and Th1/Th17 type immune response. The levels of IL-6R expressionwere increased in Th17- and Th1/Th17-dependent types of immune response, the most significant increase was observed for CD4+ cells in Th17 phenotype. Clinical features of COPD proved to be associated with the phenotypes of immune response. These results allow of specifying the inflammatory phenotype, predicting the course of chronic disease, and selecting appropriate therapy.

The effect of the combined use of polarized light and immunomodulator on the cytokine profile in patients with HPV-associated cervicitis

2021 ◽  
pp. 56-65
Author(s):  
Gulnara Grigorievna Moseshvili ◽  
Nataliya Borisovna Korchazhkina ◽  
Madina Zaudinovna Dugieva
Keyword(s):  
Immune Response ◽  
Viral Load ◽  
Comparison Group ◽  
Polarized Light ◽  
Cytokine Profile ◽  
Cervical Mucus ◽  
Control Group ◽  
Incoherent Light ◽  
Healthy Women ◽  
Combined Use

Taking into account the literature data on the significance of the mucous membranes in providing an immune filter, and cervical mucus in providing an immune response due to the high content of the main mediators of the development of a local inflammatory response, i.e. anti-inflammatory cytokines, which play a major role in the regulation of the immune response and the formation of local antiviral and antitumor immunity, we studied the cytokine profile in patients with HPV-associated cervicitis and the effect of the combined use of polarized light and an immunomodulator on their content, depending on the viral load. The purpose of the work is to study the effect of the combined exposure to blue monochromatic polarized incoherent light and polychromatic visible and infrared polarized light in combination with Imiquimod 5% cream for external use on the state of the cytokine profile in the cervical mucus in patients with HPV-associated cervicitis. Material and methods. The study included 60 patients with an HPV-associated cervicitis with the history of at least 1 year, aged 20 to 35 years, who were randomly divided into three groups: the main group of 20 patients who underwent course exposure to blue monochromatic polarized incoherent light on the projection of the carotid arteries and polychromatic visible and infrared polarized light on the cervix in combination with Imiquimod 5% cream for external use (complex 1); a comparison group of 20 patients who underwent the exposure to polychromatic visible and infrared polarized light on the cervix in combination with the topical cream, Imiquimod 5% (complex 2); a control group of 20 patients who underwent a course of local effects on the cervix with the cream Imiquimod 5% and 20 healthy women of similar age, whose the survey data were taken as a norm. To assess the cytokine state in patients with HPV-associated cervicitis, the levels of IL-1β, IL-2, IL-10, IFNa, IFNy, and TNFa in the cervical mucus were studied before and after the course of treatment by the enzyme immunoassay method. The results of the research and the discussion. Prior to the treatment, certain differences were found depending on the viral load. In patients with a low viral load, interferon levels of IFNα and IFNγ were increased by 55% (p < 0.05) and 93%, respectively (p < 0.01), compared with those of healthy women, with a significant decrease in the content of IL-10 — by 85% (p < 0.01), IL-2 — by 53% (p < 0.05) and TNFα — by 56% (p < 0.05), the content of IL-1β was increased only by 8% (p > 0.05). When analyzing cytokine levels in patients with an increased viral load, IFNα was increased by 48% (p < 0.05) and IFNγ — by 62% (p < 0.05), as well as IL-1β — by 59% (p < 0.05), and TNFα — by 37% (p < 0.05), compared to healthy women, with a significant decrease in IL-10 and IL-2 — by 53% and 56%, respectively (p < 0.05). The increase in the concentration of TNFα and IFNγ with an increased viral load was slightly lower. In patients with a significant viral load, interferons IFNα and IFNγ were increased by 35% and 40%, accordingly (p < 0.05), IL-1β — by 17.9% (p < 0.05) and IL-10 — by 14.1% against the background of a slight decrease in the content of TNFα — by 14.5% (p >0.05) and a highly significant 2.26-fold decrease in IL-2 — (p < 0.05), which play an important role in the regulation of the Th1 immune response. After the treatment, in patients of the main group (complex 1) and a comparison group (complex 2) with no significant differences, the positive dynamics was observed, manifested in lowering the initially increased concentrations of TNFα and IFNγ, IL-1β and IL-10 approaching the level of healthy individuals; in the control group, the decrease of the initially increased IL-2 and TNFα was noted, and, although there was a positive dynamics of all the studied indicators, it was less pronounced. Conclusion. The obtained data indicate a pronounced immunocorrective effect of the combined use of blue monochromatic polarized incoherent light on the projection of the carotid arteries and polychromatic visible and infrared polarized light on the cervix in combination with Imiquimod 5% cream for external use in patients with chronic cervicitis associated with papillomavirus infection, which is confirmed by an improvement in the cytokine profile.

scholarly journals Serum Glycoproteomics and Identification of Potential Mechanisms Underlying Alzheimer’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Naphatthakarn Kerdsaeng ◽  
Sittiruk Roytrakul ◽  
Suwannee Chanprasertyothin ◽  
Piangporn Charernwat ◽  
Sirintorn Chansirikarnjana ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathway ◽  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Wnt Signaling Pathway ◽  
Cytokine Signaling ◽  
Control Group ◽  
Protein Protein Interactions ◽  
Liquid Chromatography Tandem Mass

Objectives. This study compares glycoproteomes in Thai Alzheimer’s disease (AD) patients with those of cognitively normal individuals. Methods. Study participants included outpatients with clinically diagnosed AD ( N = 136 ) and healthy controls without cognitive impairment ( N = 183 ). Blood samples were collected from all participants for biochemical analysis and for Apolipoprotein   E (APOE) genotyping by real-time TaqMan PCR assays. Comparative serum glycoproteomic profiling by liquid chromatography-tandem mass spectrometry was then performed to identify differentially abundant proteins with functional relevance. Results. Statistical differences in age, educational level, and APOE ɛ3/ɛ4 and ɛ4/ɛ4 haplotype frequencies were found between the AD and control groups. The frequency of the APOE ɛ4 allele was significantly higher in the AD group than in the control group. In total, 871 glycoproteins were identified, including 266 and 259 unique proteins in control and AD groups, respectively. There were 49 and 297 upregulated and downregulated glycoproteins, respectively, in AD samples compared with the controls. Unique AD glycoproteins were associated with numerous pathways, including Alzheimer’s disease-presenilin pathway (16.6%), inflammation pathway mediated by chemokine and cytokine signaling (9.2%), Wnt signaling pathway (8.2%), and apoptosis signaling pathway (6.7%). Conclusion. Functions and pathways associated with protein-protein interactions were identified in AD. Significant changes in these proteins can indicate the molecular mechanisms involved in the pathogenesis of AD, and they have the potential to serve as AD biomarkers. Such findings could allow us to better understand AD pathology.

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