scholarly journals Relationship between Th17-mediated immunity and airway inflammation in childhood neutrophilic asthma

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Qing Wei ◽  
Jing Liao ◽  
Min Jiang ◽  
Jing Liu ◽  
Xiuan Liang ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Airway Inflammation ◽  
Th17 Cells ◽  
Mononuclear Cells ◽  
Culture Supernatant ◽  
Orphan Receptor ◽  
Th2 Cells ◽  
Healthy Children ◽  
Ki 67 ◽  
Th Cells

Abstract Background The pathogenetic mechanisms of neutrophilic asthma are not well understood now. Whether T helper (Th)17-mediated immunity contributes to the pathogenesis of neutrophilic asthma in human is still under investigation. The aim of this study was to explore the relationship between Th17-mediated immunity and airway inflammation in childhood neutrophilic asthma. Methods Twenty-eight children with exacerbated asthma and without using any glucocorticoids were divided into three groups: eosinophilic asthma (EA, n = 12) group, neutrophilic asthma (NA, n = 10) group and paucigranulocytic asthma (PGA, n = 6) group according to the induced sputum cytology. Ten healthy children were recruited as healthy control (HC, n = 10) group. Peripheral Th17 and Th2 cells, and the expression of Ki-67 in peripheral Th17 cells were detected by flow cytometry. The mRNA expression of retinoic acid-related orphan receptor γt (RORγt) in peripheral blood mononuclear cells (PBMCs) was detected by qRT-PCR. The concentrations of IL-17, IL-8 and IL-5 in sputum, as well as IL-17 in plasma and culture supernatant of activated PBMCs were measured by ELISA. Results The percentage of Th17 cells in peripheral Th cells, and the concentrations of IL-17, IL-8 in sputum, as well as IL-17 in culture supernatant of activated PBMCs were all increased in NA group, and positively correlated with neutrophil level in sputum and with each other. Also, the mRNA expression of RORγt in PBMCs and Ki-67 positivity in peripheral Th17 cells were both increased in NA group. The percentage of Th2 cells in peripheral Th cells, and the concentration of IL-5 in sputum were both increased in EA group, and positively correlated with eosinophil level in sputum and with each other. Conclusions Both Th17- and Th2-mediated immunity are involved in the pathogenesis of childhood asthma. There is predominance of Th17-mediated immunity and Th17 cells proliferation in childhood neutrophilic asthma.

scholarly journals Relationship between Th17-mediated immunity and airway inflammation in childhood neutrophilic asthma

2020 ◽  
Author(s):  
Qing Wei ◽  
Jing Liao ◽  
Min Jiang ◽  
Jing Liu ◽  
Xiuan Liang ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Airway Inflammation ◽  
Th17 Cells ◽  
Mononuclear Cells ◽  
Culture Supernatant ◽  
Orphan Receptor ◽  
Th2 Cells ◽  
Healthy Children ◽  
Ki 67 ◽  
Th Cells

Abstract Background: The pathogenetic mechanisms of neutrophilic asthma are not well understood now. Whether T helper (Th)17-mediated immunity contributes to the pathogenesis of neutrophilic asthma in human is still under investigation. The aim of this study was to explore the relationship between Th17-mediated immunity and airway inflammation in childhood neutrophilic asthma.Methods: Twenty-eight children with exacerbated asthma and without using any glucocorticoids were divided into three groups: eosinophilic asthma (EA, n=12) group, neutrophilic asthma (NA, n=10) group and paucigranulocytic asthma (PGA, n=6) group according to the induced sputum cytology. Ten healthy children were recruited as healthy control (HC, n=10) group. Peripheral Th17 and Th2 cells, and the expression of Ki-67 in peripheral Th17 cells were detected by flow cytometry. The mRNA expression of retinoic acid-related orphan receptor γt (RORγt) in peripheral blood mononuclear cells (PBMCs) was detected by qRT-PCR. The concentrations of IL-17, IL-8 and IL-5 in sputum, as well as IL-17 in plasma and culture supernatant of activated PBMCs were measured by ELISA.Results: The percentage of Th17 cells in peripheral Th cells, and the concentrations of IL-17, IL-8 in sputum, as well as IL-17 in culture supernatant of activated PBMCs were all increased in NA group, and positively correlated with neutrophil level in sputum and with each other. Also, the mRNA expression of RORγt in PBMCs and Ki-67 positivity in peripheral Th17 cells were both increased in NA group. The percentage of Th2 cells in peripheral Th cells, and the concentration of IL-5 in sputum were both increased in EA group, and positively correlated with eosinophil level in sputum and with each other.Conclusions: Both Th17- and Th2-mediated immunity are involved in the pathogenesis of childhood asthma. There is predominance of Th17-mediated immunity and Th17 cells proliferation in childhood neutrophilic asthma.

Asma neutrofílica en niños: Influencia de linfocitos Th17

2021 ◽  
pp. 1-2
Author(s):  
Ilse A. Behrends
Keyword(s):  
Mrna Expression ◽  
Th17 Cells ◽  
Mononuclear Cells ◽  
Culture Supernatant ◽  
Orphan Receptor ◽  
Th2 Cells ◽  
Healthy Children ◽  
Eosinophilic Asthma ◽  
Ki 67 ◽  
Th Cells

Background: The pathogenetic mechanims of neutrophilic asthma are not well understood now. Whether T helper (Th)17-mediated immunity contributes to the pathogenesis of neutrophilic asthma in human is still under investigation. The aim of this study was to explore the relationship between Th17-mediated immunity and airway inflammation in childhood neutrophilic asthma. Methods: Twenty-eight children with exacerbated asthma and without using any glucocorticoids were divided into three groups: eosinophilic asthma (EA, n  =  12) group, neutrophilic asthma (NA, n  =  10) group and paucigranulocytic asthma (PGA, n  =  6) group according to the induced sputum cytology. Ten healthy children were recruited as healthy control (HC, n  =  10) group. Peripheral Th17 and Th2 cells, and the expression of Ki-67 in peripheral Th17 cells were detected by flow cytometry. The mRNA expression of retinoic acid-related orphan receptor γt (RORγt) in peripheral blood mononuclear cells (PBMCs) was detected by qRT-PCR. The concentrations of IL-17, IL-8 and IL-5 in sputum, as well as IL-17 in plasma and culture supernatant of activated PBMCs were measured by ELISA. Results: The percentage of Th17 cells in peripheral Th cells, and the concentrations of IL-17, IL-8 in sputum, as well as IL-17 in culture supernatant of activated PBMCs were all increased in NA group, and positively correlated with neutrophil level in sputum and with each other. Also, the mRNA expression of RORγt in PBMCs and Ki-67 positivity in peripheral Th17 cells were both increased in NA group. The percentage of Th2 cells in peripheral Th cells, and the concentration of IL-5 in sputum were both increased in EA group, and positively correlated with eosinophil level in sputum and with each other. Conclusions: Both Th17- and Th2-mediated immunity are involved in the pathogenesis of childhood asthma. There is predominance of Th17-mediated immunity and Th17 cells proliferation in childhood neutrophilic asthma.

scholarly journals Relationship between Th17-mediated immunity and airway inflammation in childhood neutrophilic asthma

2020 ◽  
Author(s):  
Qing Wei ◽  
Jing Liao ◽  
Min Jiang ◽  
Jing Liu ◽  
Xiuan Liang ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Airway Inflammation ◽  
Th17 Cells ◽  
Culture Supernatant ◽  
Th2 Cells ◽  
Healthy Children ◽  
Eosinophilic Asthma ◽  
Ki 67 ◽  
Th Cells ◽  
Healthy Control

Abstract Background The pathogenetic mechanisms of neutrophilic asthma are not well understood now. Whether Th17-mediated immunity contributes to the pathogenesis of neutrophilic asthma in human is still under investigation. The aim of this study was to explore the relationship between Th17-mediated immunity and airway inflammation in childhood neutrophilic asthma. Methods Twenty-eight children with exacerbated asthma and without using any glucocorticoids were divided into three groups: eosinophilic asthma (EA) group, neutrophilic asthma (NA) group and paucigranulocytic asthma (PGA) group according to the induced sputum cytology. Ten healthy children were recruited as healthy control (HC) group. Peripheral Th17 and Th2 cells, and the expression of Ki-67 in peripheral Th17 cells were detected by flow cytometry. The mRNA expression of RORγt in PBMCs was detected by qRT-PCR. The concentrations of IL-17, IL-8 and IL-5 in sputum, as well as IL-17 in plasma and culture supernatant of activated PBMCs were measured by ELISA. Results The percentage of Th17 cells in peripheral Th cells, and the concentrations of IL-17, IL-8 in sputum, as well as IL-17 in culture supernatant of activated PBMCs were all increased in NA group, and positively correlated with neutrophil level in sputum and with each other. Also, the mRNA expression of RORγt in PBMCs and Ki-67 positivity in peripheral Th17 cells were both increased in NA group. The percentage of Th2 cells in peripheral Th cells, and the concentration of IL-5 in sputum were both increased in EA group, and positively correlated with eosinophil level in sputum and with each other. Conclusions Both Th17- and Th2-mediated immunity are involved in the pathogenesis of childhood asthma. There is predominance of Th17-mediated immunity and Th17 cells proliferation in childhood neutrophilic asthma.

scholarly journals Effect of interleukin (IL)-35 on IL-17 expression and production by human CD4+ T cells

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e2999 ◽  
Author(s):  
Kosuke Okada ◽  
Takeki Fujimura ◽  
Takeshi Kikuchi ◽  
Makoto Aino ◽  
Yosuke Kamiya ◽  
...  
Keyword(s):  
T Cells ◽  
Mrna Expression ◽  
Th17 Cells ◽  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Quantitative Polymerase Chain Reaction ◽  
Orphan Receptor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Cytokine Cocktail

Background Interleukin (IL)-17 produced by mainly T helper 17 (Th17) cells may play an important destructive role in chronic periodontitis (CP). Thus, anti-inflammatory cytokines, such as IL-35, might have a beneficial effect in periodontitis by inhibiting differentiation of Th17 cells. Th17 differentiation is regulated by the retinoic acid receptor-related orphan receptor (ROR) α (encoded by RORA) and RORγt (encoded by RORC). However, the role of IL-35 in periodontitis is not clear and the effect of IL-35 on the function of Th17 cells is still incompletely understood. Therefore, we investigated the effects of IL-35 on Th17 cells. Methods Peripheral blood mononuclear cells (PBMCs) were sampled from three healthy volunteers and three CP patients and were analyzed by flow cytometry for T cell population. Th17 cells differentiated by a cytokine cocktail (recombinant transforming growth factor-β, rIL-6, rIL-1β, anti-interferon (IFN)-γ, anti-IL-2 and anti-IL-4) from PBMCs were cultured with or without rIL-35. IL17A (which usually refers to IL-17), RORA and RORCmRNA expression was analyzed by quantitative polymerase chain reaction, and IL-17A production was determined by enzyme-linked immunosorbent assay. Results The proportion of IL-17A+CD4+ slightly increased in CP patients compared with healthy controls, however, there were no significant differences in the percentage of IL-17A+CD4+ as well as IFN-γ+CD4+ and Foxp3+CD4+ T cells between healthy controls and CP patients. IL17A, RORA and RORC mRNA expression was significantly increased in Th17 cells induced by the cytokine cocktail, and the induction was significantly inhibited by addition of rIL-35 (1 ng/mL). IL-17A production in Th17 cells was significantly inhibited by rIL-35 addition (1 ng/mL). Discussion The present study suggests that IL-35 could directly suppress IL-17 expression via RORα and RORγt inhibition and might play an important role in inflammatory diseases such as periodontitis.

scholarly journals Role of Th17 Cells in Skin Inflammation of Allergic Contact Dermatits

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Matthias Peiser
Keyword(s):  
T Cells ◽  
Th17 Cells ◽  
Skin Diseases ◽  
Inflammatory Diseases ◽  
Retinoic Acid Receptor ◽  
Contact Hypersensitivity ◽  
Orphan Receptor ◽  
Th2 Cells ◽  
Th Cells ◽  
Allergic Contact

Extending the classical concept considering an imbalance exclusively of T helper(h) 1 and Th2 cells on the bottom of many inflammatory diseases, Th17 cells were recently described. Today, there is sufficient experimental evidence to classify psoriasis and allergic contact dermatitis (ACD) amongst other inflammatory skin disorders as IL-17 associated diseases. In several human studies, T-cell-clones could be isolated from eczema biopsies, and high IL-17 levels were observed after challenge with allergen. In the last years, the phenotype of these IL-17 releasing T cells was in the focus of discussion. It has been suggested that Th17 could be identified by expression of retinoic acid receptor-related orphan receptor (ROR)C (humans) or RORγt (mice) and IL-17, accompanied by the absence of IFN-γand IL-22. In cells from skin biopsies, contact allergens elevate IL-17A, IL-23, and RORC within the subset of Th cells. The indications for a participation of Th17 in the development of ACD are supported by data from IL-17 deficient mice with reduced contact hypersensitivity (CHS) reactions that could be restored after transplantation of wild type CD4+T cells. In addition to Th17 cells, subpopulations of CD8+T cells and regulatory T cells are further sources of IL-17 that play important roles in ACD as well. Finally, the results from Th17 cell research allow today identification of different skin diseases by a specific profile of signature cytokines from Th cells that can be used as a future diagnostic tool.

Regulation of IL-17 in chronic inflammation in the human lung

2011 ◽  
Vol 120 (12) ◽  
pp. 515-524 ◽  
Author(s):  
Carol Pridgeon ◽  
Laurence Bugeon ◽  
Louise Donnelly ◽  
Ursula Straschil ◽  
Susan J. Tudhope ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lung Tissue ◽  
Mononuclear Cells ◽  
Human Lung ◽  
Treg Cells ◽  
Orphan Receptor ◽  
Th2 Cells ◽  
Chronic Obstructive ◽  
Interleukin 17

The regulation of human Th17 cell effector function by Treg cells (regulatory T-cells) is poorly understood. In the present study, we report that human Treg (CD4+CD25+) cells inhibit the proliferative response of Th17 cells but not their capacity to secrete IL (interleukin)-17. However, they could inhibit proliferation and cytokine production by Th1 and Th2 cells as determined by IFN-γ (interferon-γ) and IL-5 biosynthesis. Currently, as there is interest in the role of IL-17-producing cells and Treg cells in chronic inflammatory diseases in humans, we investigated the presence of CD4+CD25+ T-cells and IL-17 in inflammation in the human lung. Transcripts for IL-17 were expressed in mononuclear cells and purified T-cells from lung tissue of patients with chronic pulmonary inflammation and, when activated, these cells secrete soluble protein. The T-cell-specific transcription factors RORCv2 (retinoic acid-related orphan receptor Cv2; for Th17) and FOXP3 (forkhead box P3; for Treg cells) were enriched in the T-cell fraction of lung mononuclear cells. Retrospective stratification of the patient cohort into those with COPD (chronic obstructive pulmonary disease) and non-COPD lung disease revealed no difference in the expression of IL-17 and IL-23 receptor between the groups. We observed that CD4+CD25+ T-cells were present in comparable numbers in COPD and non-COPD lung tissue and with no correlation between the presence of CD4+CD25+ T-cells and IL-17-producing cells. These results suggest that IL-17-expressing cells are present in chronically inflamed lung tissue, but there is no evidence to support this is due to the recruitment or expansion of Treg cells.

scholarly journals Xianfanghuomingyin, a Chinese Compound Medicine, Modulates the Proliferation and Differentiation of T Lymphocyte in a Collagen-Induced Arthritis Mouse Model

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Bo Nie ◽  
Xue Li ◽  
Yi Wei ◽  
Meng Chen ◽  
Jingwei Zhou ◽  
...  
Keyword(s):  
Mouse Model ◽  
Th17 Cells ◽  
Retinoic Acid Receptor ◽  
Treg Cells ◽  
Immunological Tolerance ◽  
Cartilage Destruction ◽  
Orphan Receptor ◽  
Th2 Cells ◽  
Collagen Induced Arthritis ◽  
Proliferation And Differentiation

In traditional Chinese medicine (TCM), xianfanghuomingyin (XFHM) is used to treat autoimmune diseases, including rheumatoid arthritis (RA). Here, we studied the mechanisms underlying its treatment effects, especially its anti-inflammatory effects in a collagen-induced arthritis (CIA) mouse model. We found that cartilage destruction and pannus formation were alleviated by treatment with XFHM. The abnormal differentiation of Th1 and Th17 cells was downregulated significantly by XFHM, and Th2 and Treg cells were upregulated. Moreover, the expression levels of specific cytokines and transcription factors related to Th1 cells (interferonγ[IFNγ], T-bet) and Th17 cells (interleukin- [IL-] 17) and the nuclear receptor retinoic acid receptor-related orphan receptor-gamma (RORγ) were downregulated. Serum IL-4 and GATA-3, which contribute to Th2 cells differentiation, increased significantly after XFHM administration. These results indicate that XFHM can restore the balance of T lymphocytes and reestablish the immunological tolerance to inhibit autoinflammatory disorder of RA. Taken together, XFHM can be used as a complementary or alternative traditional medicine to treat RA.

scholarly journals Critical Involvement of CD44 in T Helper Type 2 Cell-Mediated Eosinophilic Airway Inflammation in a Mouse Model of Acute Asthma

2022 ◽  
Vol 12 ◽  
Author(s):  
Shigeki Katoh
Keyword(s):  
Monoclonal Antibodies ◽  
Airway Inflammation ◽  
Th17 Cells ◽  
Acute Asthma ◽  
Mite Allergen ◽  
Th2 Cells ◽  
T Helper ◽  
Th2 Cell ◽  
Helper Type

Interactions between CD44 and hyaluronan (HA) are crucial for recruiting leukocytes to inflamed tissues. This review summarizes findings from our studies of the roles of CD44-HA interactions in leukocyte trafficking, with a particular focus on airway T helper type 2 (Th2) cells in mouse models of acute asthma. In a mite allergen-induced model of acute asthma, intraperitoneal injection of anti-CD44 monoclonal antibodies blocked lymphocytes and eosinophils from accumulating in the lung, and suppressed both the antigen-induced increase in Th2 cytokines in the bronchoalveolar lavage fluid (BALF) and airway hyperresponsiveness (AHR). CD44 deficiency was associated with decreased mite allergen-induced Th2 cell-mediated airway inflammation and AHR in sensitized mice. Asthmatic responses to antigen-sensitized splenic CD4+ T cells transferred from CD44-deficient mice were weaker than in wild-type mice. Administration of anti-CD44 monoclonal antibodies preferentially suppressed the airway accumulation of antigen-specific Th2 cells induced by antigen challenge, without affecting Th1 and Th17 cells. Increased HA-binding ability of CD44 and expression of Neu1 sialidase were observed on antigen-specific Th2 cells compared with antigen-specific Th1 and Th17 cells. Finally, in a mouse model of acute asthma, neuraminidase 1-deficient SM/J mice exhibited a lower Th2 cytokine concentration and a lower absolute Th2 cell number in the BALF, as well as an attenuated AHR. Our findings indicate that CD44 critically contributes to the antigen challenge-induced airway accumulation of antigen-specific Th2 cells, without affecting Th1 and Th17 cells, in mice. Furthermore, neuraminidase 1 activity is necessary for the interaction between HA and CD44, and Th2 cell-mediated airway inflammation.

scholarly journals JIA patient T cells differentiate into Th1, Th17 and Th1.17 effector cells under Th1 polarizing conditions

2021 ◽  
Author(s):  
Anna E Patrick ◽  
Tashawna Esmond ◽  
Kayla Shoaff ◽  
David M Patrick ◽  
David K Flaherty ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cell ◽  
Cell Cultures ◽  
Th17 Cells ◽  
Mononuclear Cells ◽  
Healthy Children ◽  
Th1 Cell ◽  
Peripheral Blood Mononuclear ◽  
Ifn Gamma

Objective. T helper cells develop into discrete Th1, Th2 or Th17 lineages that selectively express IFN-gamma, IL-4/IL-5/IL-13, or IL-17, respectively and actively silence signature cytokines expressed by opposing lineages. Our objective was to compare Th1, Th2 and Th17 polarization in cell culture models using JIA patient samples. Methods. Peripheral blood mononuclear cells were isolated from JIA or healthy prepubescent children. T cell naive and memory phenotypes were assessed by flow cytometry. T cell proliferation was measured using a fluorescence-based assay. Th cell cultures were generated in vitro and IFN-gamma, IL-17, and TNF-alpha measured by ELISA and flow cytometry. Results. JIA Th1 cells produced increased IFN-gamma and inappropriately produced IL-17. JIA Th17 cells produced increased IL-17. JIA Th1 cell cultures develop dual producers of IFN-gamma and IL-17, which are Th1.17 cells. JIA Th1 cultures expressed elevated levels of both T-bet and ROR-gamma-T. RNA sequencing confirmed activation of immune responses and inappropriate activation of IL-17 signaling pathways in Th1 cultures. A subset of JIA patient samples was disproportionally responsible for the enhanced IFN-gamma and IL-17 phenotype and Th1.17 phenotype. Conclusions. This study reveals that JIA patient uncommitted T cell precursors, but not healthy children, inappropriately develop into inflammatory effector Th1.17 and Th17 cells under Th1 polarizing conditions.

scholarly journals Trans-10, cis-12-conjugated linoleic acid increases phagocytosis of porcine peripheral blood polymorphonuclear cells in vitro

2007 ◽  
Vol 97 (1) ◽  
pp. 117-125 ◽  
Author(s):  
Ji-Houn Kang ◽  
Geun-Shik Lee ◽  
Eui-Bae Jeung ◽  
Mhan-Pyo Yang
Keyword(s):  
Linoleic Acid ◽  
Mrna Expression ◽  
Conjugated Linoleic Acid ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Culture Supernatant ◽  
Supernatant Fraction ◽  
Polymorphonuclear Cells ◽  
Phagocytic Capacity ◽  
Tnf Α

Trans-10, cis-12-conjugated linoleic acid (t10c12-CLA) has been shown to alter immune function. PPARγ has been shown to potentially play an important role in regulating inflammatory and immune responses by modulating the activity of monocytes and macrophages. Previous studies have indicated that the phagocytic capacity of porcine peripheral blood polymorphonuclear cells (PMN) was enhanced by the culture supernatant fraction from t10c12-CLA-stimulated porcine peripheral blood mononuclear cells (PBMC) but not by t10c12-CLA itself. In the present study, we examined the effects of t10c12-CLA on PPARγ and TNF-α expression of porcine PBMC and the phagocytic capacity of PMN. t10c12-CLA increased TNF-α mRNA expression and production by PBMC. The phagocytic capacity of porcine PMN was enhanced by either culture supernatant fraction from PBMC treated with t10c12-CLA or recombinant porcine (rp) TNF-α. Anti-rpTNF-α polyclonal antibody inhibited the enhancement of PMN phagocytic capacity. t10c12-CLA also up regulated PPARγ mRNA expression in porcine PBMC. Bisphenol A diglycidyl ether, a PPARγ antagonist, not only completely negated the t10c12-CLA-stimulating effects on TNF-α expression and production by porcine PBMC, but also decreased the enhancement of PMN phagocytic capacity by the t10c12-CLA-stimulated porcine PBMC culture supernatant fraction. These results suggest that t10c12-CLA has an immunostimulating effect on porcine PMN phagocytic capacity, which is mediated by TNF-α from PBMC via a PPARγ-dependent pathway.

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