TH1, TH2, and TH17 cells instruct monocytes to differentiate into specialized dendritic cell subsets

Abstract Monocytes and T helper (TH) cells rapidly infiltrate inflamed tissues where monocytes differentiate into inflammatory dendritic cells (DCs) through undefined mechanisms. Our studies indicate that TH cells frequently interact with monocytes in inflamed skin and elicit the differentiation of specialized DC subsets characteristic of these lesions. In psoriasis lesions, TH1 and TH17 cells interact with monocytes and instruct these cells to differentiate into TH1- and TH17-promoting DCs, respectively. Correspondingly, in acute atopic dermatitis, TH2 cells interact with monocytes and elicit the formation of TH2-promoting DCs. DC formation requires GM-CSF and cell contact, whereas TH subset specific cytokines dictate DC function and the expression of DC subset specific surface molecules. Moreover, the phenotypes of T cell–induced DC subsets are maintained after subsequent stimulation with a panel of TLR agonists, suggesting that TH-derived signals outweigh downstream TLR signals in their influence on DC function. These findings indicate that TH cells govern the formation and function of specialized DC subsets.

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Th17 Cells and Associated Cytokines in Inflammation and Cancer

Blood ◽

10.1182/blood.v118.21.sci-5.sci-5 ◽

2011 ◽

Vol 118 (21) ◽

pp. SCI-5-SCI-5

Author(s):

Chen Dong

Keyword(s):

T Cells ◽

Germinal Center ◽

Th17 Cells ◽

The Other ◽

Th Cells ◽

Tissue Inflammation ◽

Tfh Cells ◽

Follicular Helper ◽

And Function ◽

Th1 And Th2

Abstract Abstract SCI-5 CD4+ T cells, upon activation, differentiate into cytokine-producing effector helper T (TH) cells. In addition to TH1 and TH2 lineage cells, additional TH subsets, including TH17 and T follicular helper (Tfh) cells have been identified. TH17 cells produce IL-17, IL-17F, IL-21, and IL-22 and mediate tissue inflammation. TH17 cells play protective or pathogenic roles in cancer, depending on the context. On the other hand, Tfh cells produce IL-21 and regulate germinal center reactions. Tfh cells may play a role in some forms of lymphoma. I will discuss on the regulation and function of these two subsets of T cells in the context of cancer. Disclosures: Dong: Ono: Consultancy; Tempero: Consultancy; Genentech: Honoraria; GSK: Consultancy; AnaptysBio: Consultancy.

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

10.21203/rs.3.rs-38358/v2 ◽

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.

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

10.21203/rs.3.rs-38358/v1 ◽

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.

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ROG Negatively Regulates T-Cell Activation but Is Dispensable for Th-Cell Differentiation

Molecular and Cellular Biology ◽

10.1128/mcb.25.2.554-562.2005 ◽

2005 ◽

Vol 25 (2) ◽

pp. 554-562 ◽

Cited By ~ 26

Author(s):

Bok Yun Kang ◽

Shi-Chuen Miaw ◽

I-Cheng Ho

Keyword(s):

T Cells ◽

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Target Gene ◽

Interleukin 2 ◽

Negative Regulator ◽

Th2 Cells ◽

Th Cells ◽

And Function

ABSTRACT ROG, a transcriptional repressor, is a direct target gene of NF-AT and a putative negative regulator of T-cell activation. In addition, overexpression of ROG suppresses the activity of GATA-3, implying a role of ROG in the differentiation and function of Th cells. Despite these observations, the function of ROG has yet to be confirmed by loss-of-function approaches. Here we report that ROG-deficient T cells are hypersensitive to anti-CD3 stimulation and produce more interleukin-2 (IL-2) due to enhanced NF-κB activity. ROG-deficient dendritic cells also produce more IL-12p40, another NF-κB target gene. However, ROG-deficient Th cells are capable of differentiating into Th1 and Th2 cells, and ROG-deficient mice have no defect in mounting appropriate Th immune responses in vivo. Thus, ROG is dispensable for the differentiation and function of Th cells but serves as a mediator of NF-AT-initiated suppression of NF-κB. Its mechanism of action and its expression pattern are distinct from those of other transcription factors negatively regulating the activation of T cells.

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

Allergy Asthma & Clinical Immunology ◽

10.1186/s13223-020-00504-3 ◽

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.

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GATA3 up-regulation associated with surface expression of CD294/CRTH2: a unique feature of human Th cells

Blood ◽

10.1182/blood-2006-05-025940 ◽

2007 ◽

Vol 109 (10) ◽

pp. 4343-4350 ◽

Cited By ~ 29

Author(s):

Umberto De Fanis ◽

Francesca Mori ◽

Rebecca J. Kurnat ◽

Won Kyung Lee ◽

Maria Bova ◽

...

Keyword(s):

Cell Function ◽

Surface Expression ◽

Th2 Cells ◽

Specific Expression ◽

Th Cells ◽

T Box ◽

Th Cell ◽

Ifn Γ ◽

Additional Level ◽

And Function

Abstract GATA-3 and T-box expressed in T cells (T-bet) play central roles in Th-cell development and function. Consistently, studies in mice document their selective expression in Th1 and Th2 cells, respectively. In contrast, it is not clear whether these genes are regulated in human Th cells. Here we show that T-bet expression is polarized to a comparable degree in human and mouse Th-cell cultures, while only mouse GATA3 is subject to substantial regulation. This did not reflect differential skewing efficiency in human versus mouse cultures, as these contained similar frequencies of IFN-γ– and IL-4–producing cells. However, GATA-3 was expressed at significantly higher levels in human IL-4–producing cells enriched via capture with monoclonal antibodies (mAbs) against the PGD2 receptor, CRTH2, the best selective Th2-cell surface marker to date. Along with increased IL-4 and GATA-3, CRTH2+ Th cells isolated from Th2-skewed cultures or the circulating memory pool exhibited markedly decreased IFN-γ and T-bet expression. Thus, the human GATA-3 gene is not regulated in response to polarizing signals that are sufficient to direct Th2-specific expression in mouse cells. This postulates the involvement of an additional level of complexity in the regulation of human GATA-3 expression and stresses the existence of nontrivial differences in the regulation of human versus mouse T-cell function.

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Asma neutrofílica en niños: Influencia de linfocitos Th17

Karger Kompass Neumología ◽

10.1159/000515761 ◽

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.

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The role of B cells in regulation of Th cell differentiation in Coxsackievirus B3-Induced Acute Myocarditis

10.21203/rs.3.rs-169159/v1 ◽

2021 ◽

Author(s):

Zhihong Cen ◽

Yong Li ◽

Bin Wei ◽

Weifeng Wu ◽

Yanlan Huang ◽

...

Keyword(s):

Cell Differentiation ◽

B Cells ◽

B Cell ◽

Th17 Cells ◽

Th2 Cells ◽

Cardiac Damage ◽

Th Cells ◽

Th22 Cells ◽

Th Cell

Abstract Background:Viral myocarditis (VMC) is the major cause of sudden death in adolescents. To date, no effective treatment has been identified for VMC. Studies have shown that T helper (Th) cells such as Th1, Th2, Th17, and Th22 cells are involved in the pathogenesis of VMC. However, the role of B cells and their impact on Th cells in VMC is unclear. In this study, we investigated the role of B cells in Th cell differentiation in myocardial damage in an animal model of VMC.Methods and Results:C57BL/6 mice were infected with Coxsackievirus B3 (CVB3) intraperitoneally or injected with phosphate-buffered saline as a control condition. At day 7, samples from these mice were analyzed by histology, ELISA, flow cytometry, and gene expression assays. We found that TNF-α-, IL-6-, and IL-17-producing B cell numbers were significantly increased, while IL-4-producing B cell population was significantly reduced in acute VMC. Furthermore, we performed B cell knockout (BKO), SCID, and SCID+B cells reconstitution experiments. We found that BKO alleviated the cardiac damage following CVB3 infection, may hamper the differentiation of Th1 and Th17 cells, may promote the differentiation of Th2 cells, and proved ineffective for the differentiation of Th22 cells. In contrast, SCID+B cells reconstitution experiment exacerbated the cardiac damage. Ex vivo studies further revealed that B cells promote the differentiation of Th1 and Th17 cells and inhibit the differentiation of Th2 cells.Conclusions:Our study shows that B cells are activated and have strong abilities of antigen presentation and producing cytokines in VMC; B cells not only play a pathogenic role in VMC independent of T cells, but also promote Th1 and Th17 cell differentiation, and hamper Th2 cell differentiation in VMC.

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STAT Family Protein Expression and Phosphorylation State during moDC Development Is Altered by Platinum-Based Chemotherapeutics

Journal of Immunology Research ◽

10.1155/2019/7458238 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 2

Author(s):

Nienke de Haas ◽

Coco de Koning ◽

Stefania di Blasio ◽

Georgina Flórez-Grau ◽

I. Jolanda M. de Vries ◽

...

Keyword(s):

Signaling Pathway ◽

Platinum Drugs ◽

Comprehensive Overview ◽

Phosphorylation State ◽

Stat Proteins ◽

Gm Csf ◽

Dc Function ◽

Stat Signaling ◽

Important Regulator ◽

And Function

The STAT signaling pathway is important in dendritic cell (DC) development and function. Tumor cells can induce STAT signaling, thereby inhibiting DC maturation and immunostimulatory functions, leading to hampered efficacy of DC-based immunotherapies. Platinum-based chemotherapeutics can inhibit STAT signaling, thereby making them an interesting tool to improve DC development and function. In this study, we provide a comprehensive overview of STAT expression and phosphorylation during DC differentiation and maturation and investigate the effects of platinum drugs on STAT signaling during these processes. Monocytes were differentiated into monocyte-derived DCs (moDCs) with IL-4 and GM-CSF and matured with cytokines or TLR ligands. STAT expression and phosphorylation were analyzed by western blotting, and moDC viability and phenotype were analyzed by flow cytometry. Platinum drugs were added at day 3 of differentiation or at the start of maturation to investigate regulation of the STAT signaling pathway. All STAT proteins were expressed during moDC differentiation and STAT1, STAT5, and STAT6 were phosphorylated. No significant changes occurred in the expression and phosphorylation state of the STAT proteins during differentiation. After maturation with TLR ligands, the expression of STAT1 increased, but other STAT proteins were not affected. Phosphorylation of STAT1 and STAT3 increased during maturation, where TLR ligands induced significantly higher levels of phosphorylation than cytokines. Platinum drugs cisplatin and oxaliplatin significantly inhibited phosphorylation of STAT6 during differentiation and maturation. Treatment did not affect the phenotype or viability of the cells. As STAT6 is an important regulator of DC function, these findings suggest a role for platinum-based chemotherapeutics to enhance DC function via inhibition of STAT signaling, thereby potentially enhancing efficacy of DC-based immunotherapies.

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Interferon-β Intensifies Interleukin-23-Driven Pathogenicity of T Helper Cells in Neuroinflammatory Disease

Cells ◽

10.3390/cells10082139 ◽

2021 ◽

Vol 10 (8) ◽

pp. 2139

Author(s):

Agnieshka Agasing ◽

James L. Quinn ◽

Gaurav Kumar ◽

Robert C. Axtell

Keyword(s):

T Helper Cells ◽

Th17 Cells ◽

T Helper ◽

Interferon Β ◽

Gm Csf ◽

Neuroinflammatory Disease ◽

Th 17 ◽

Th17 Differentiation ◽

Interleukin 23 ◽

And Function

Interferon (IFN)-β is a popular therapy for multiple sclerosis (MS). However, 25–40% of patients are nonresponsive to this therapy, and it worsens neuromyelitis optica (NMO), another neuroinflammatory disease. We previously identified, in both NMO patients and in mice, that IFN-β treatment had inflammatory effects in T Helper (TH) 17-induced disease through the production of the inflammatory cytokine IL-6. However, other studies have shown that IFN-β inhibits the differentiation and function of TH17 cells. In this manuscript, we identified that IFN-β had differential effects on discrete stages of TH17 development. During early TH17 development, IFN-β inhibits IL-17 production. Conversely, during late TH17 differentiation, IFN-β synergizes with IL-23 to promote a pathogenic T cell that has both TH1 and TH17 characteristics and expresses elevated levels of the potent inflammatory cytokines IL-6 and GM-CSF and the transcription factor BLIMP. Together, these findings help resolve a paradox surrounding IFN-β and TH17-induced disease and illuminate the pathways responsible for the pathophysiology of NMO and MS patients who are IFN-β nonresponders.

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