scholarly journals The Role of Th17 Response in COVID-19

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1550
Author(s):  
Diana Martonik ◽  
Anna Parfieniuk-Kowerda ◽  
Magdalena Rogalska ◽  
Robert Flisiak
Keyword(s):  
Immune Response ◽  
Treg Cells ◽  
The Body ◽  
System Response ◽  
Th17 Response ◽  
Monocyte Chemoattractant Protein 1 ◽  
Acute Infectious Disease ◽  
Cytokine Cascade ◽  
Necrosis Factor

COVID-19 is an acute infectious disease of the respiratory system caused by infection with the SARS-CoV-2 virus (Severe Acute Respiratory Syndrome Coronavirus 2). Transmission of SARS-CoV-2 infections occurs through droplets and contaminated objects. A rapid and well-coordinated immune system response is the first line of defense in a viral infection. However, a disturbed and over-activated immune response may be counterproductive, causing damage to the body. Severely ill patients hospitalised with COVID-19 exhibit increased levels of many cytokines, including Interleukin (IL)-1β, IL-2, IL-6, IL-7, IL-8, IL-10, IL-17, granulocyte colony stimulating factor (G-CSF), monocyte chemoattractant protein 1 (MCP-1) and tumor necrosis factor (TNF). Increasing evidence suggests that Th17 cells play an important role in the pathogenesis of COVID-19, not only by activating cytokine cascade but also by inducing Th2 responses, inhibiting Th1 differentiation and suppressing Treg cells. This review focuses on a Th17 pathway in the course of the immune response in COVID-19, and explores plausible targets for therapeutic intervention.

scholarly journals HIF1α/TET1 Pathway Mediates Hypoxia-Induced Adipocytokine Promoter Hypomethylation in Human Adipocytes

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 134 ◽  
Author(s):  
Mohamed M. Ali ◽  
Shane A. Phillips ◽  
Abeer M. Mahmoud
Keyword(s):  
Dna Methylation ◽  
Interleukin 1 ◽  
Hypoxia Inducible Factor ◽  
Interferon Γ ◽  
The Body ◽  
Human Adipocytes ◽  
Protein Levels ◽  
Factor Α ◽  
Necrosis Factor

Obesity is associated with the accumulation of dysfunctional adipose tissue that secretes several pro-inflammatory cytokines (adipocytokines). Recent studies have presented evidence that adipose tissues in obese individuals and animal models are hypoxic, which may result in upregulation and stabilization of the hypoxia inducible factor HIF1α. Epigenetic mechanisms such as DNA methylation enable the body to respond to microenvironmental changes such as hypoxia and may represent a mechanistic link between obesity-associated hypoxia and upregulated inflammatory adipocytokines. The purpose of this study was to investigate the role of hypoxia in modifying adipocytokine DNA methylation and subsequently adipocytokine expression. We suggested that this mechanism is mediated via the DNA demethylase, ten-eleven translocation-1 (TET1), transcription of which has been shown to be induced by HIF1α. To this end, we studied the effect of hypoxia (2% O2) in differentiated subcutaneous human adipocytes in the presence or absence of HIF1α stabilizer (Dimethyloxalylglycine (DMOG), 500 μM), HIF1α inhibitor (methyl 3-[[2-[4-(2-adamantyl) phenoxy] acetyl] amino]-4-hydroxybenzoate, 30 μM), or TET1-specific siRNA. Subjecting the adipocytes to hypoxia significantly induced HIF1α and TET1 protein levels. Moreover, hypoxia induced global hydroxymethylation, reduced adipocytokine DNA promoter methylation, and induced adipocytokine expression. These effects were abolished by either HIF1α inhibitor or TET1 gene silencing. The major hypoxia-responsive adipocytokines were leptin, interleukin-1 (IL6), IL1β, tumor necrosis factor α (TNFα), and interferon γ (IFNγ). Overall, these data demonstrate an activation of the hydroxymethylation pathway mediated by TET1. This pathway contributes to promoter hypomethylation and gene upregulation of the inflammatory adipocytokines in adipocytes in response to hypoxia.

Plasmacytoid Dendritic Cells (PDC) and Th17 Immune Response Contribution in Gut Acute Graft-Versus-Host-Disease (GVHD)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2968-2968
Author(s):  
Florent Malard ◽  
Céline Bossard ◽  
Jessy Arbez ◽  
Patrice Chevallier ◽  
Thierry Guillaume ◽  
...  
Keyword(s):  
Immune Response ◽  
Stem Cell ◽  
Autoimmune Diseases ◽  
Intestinal Mucosa ◽  
Th17 Cells ◽  
Acute Gvhd ◽  
Type I ◽  
Type I Ifn ◽  
Th17 Response

Abstract Abstract 2968 Background. Acute GVHD after allogeneic stem cell transplantation (allo-SCT) is an exaggerated immune response against alloantigens involving dysregulation of inflammatory cytokine cascades. Previous studies established an important role of Th1 cells in acute GVHD pathophysiology. However, the identification of proinflammatory Th17 cells which contribute to autoimmune diseases pathophysiology, raised the issue of the role of Th17 cells in human acute GVHD. Indeed, the contribution of Th17 cells in acute GVHD was assessed in GVHD mouse models with conflicting results. In addition, the role of the PDC subset (the professional type I IFN-secreting cells), which play an important role in triggering Th17-related cytokines and autoimmune diseases, is not yet established in the acute GVHD setting. This report investigated the role of Th17 cells and their interaction with PDC in gastrointestinal (GI) biopsies taken from patients with or without acute GVHD. Patients and Methods. Studies described in this report were performed in a single centre series of 21 patients who underwent allo-SCT for different hematological malignancies (n=19) and severe aplastic anemia (n=2). The median age of patients was 53 years (range, 16–69). The stem cell source was PBSCs in 19 cases (85%), CB in 2 cases and BM in one case. Ten patients received transplant from a matched-related donor, and 11 patients from a matched-unrelated donor. A reduced-intensity conditioning regimen was used in the majority of cases (n=19; 90%) Immunohistochemistry was performed on deparaffinized tissues sections using an indirect immunoperoxydase method. A quantitative evaluation of antigens expression was performed by counting the number of positive cells in the whole biopsy at 200 magnifications for each sample. Results. In this cohort, based on standard pathology criteria, 16 patients had a histologically proven gastrointestinal acute GVHD. In all cases, biopsies were taken before initiation of systemic corticosteroid therapy. The remaining 5 patients did not have histological signs of acute GVHD (and did not develop clinical signs of acute GVHD) and thus, were used as controls. In order to identify the Th17 cell population, biopsies were tested for expression of the CD161 and CCR6 markers, and ROR-gamma-t, the key transcription factor that orchestrates the differentiation of Th17 cells. Significantly higher numbers of ROR-gamma-t+ and CD161+ cells were counted in the intestinal mucosa of patients with acute GVHD compared with intestinal mucosa of patients without acute GVHD, mainly found in the lamina propria but also in the epithelium of altered glands (p=0.016 and p=0.009 for ROR-gamma-t and CD161 expression respectively). Given the role of PDCs in triggering Th17-related cytokines, we sought next to determine the proportion of PDCs in intestinal biopsies from these same patients. This analysis showed a significant increase of CD123+ PDCs in the intestinal mucosa of patients with acute GVHD compared with mucosa of patients without acute GVHD (p=0.017). Moreover, we observed a significant correlation between the number of CD123+ PDCs and ROR-gamma-t or CD161 expressing cells in the intestinal mucosa of acute GVHD patients, highlighting the link between PDC and Th17 cells. Conclusion. The current study shed some light on the role of Th17 cells in the context of gastro-intestinal acute GVHD. Using well-established specific markers, we show that Th17 cells infiltrate intestinal biopsies from patients with acute GVHD. In addition, Th17 infiltration was paralleled by the infiltration of PDCs, suggesting a potential new pathophysiological link between PDCs and Th17 response in the context of gastro-intestinal acute GVHD. This is consistent with studies showing that PDCs can drive the differentiation of Th17 cells. Functional analyses are currently ongoing. Although the exact mechanism that links type I IFN production to PDC-mediated Th17 responses is still unclear in acute GVHD, these data raise the prospect of future innovative approaches to optimize immunosuppression regimens for the treatment or prophylaxis of acute GVHD by targeting PDCs and the Th17 response. Disclosures: No relevant conflicts of interest to declare.

scholarly journals IMMUNE MECHANISMS FOR DEVELOPMENT OF CONTROLLED AND PARTIALLY CONTROLLED ASTHMA

2019 ◽  
Vol 21 (3) ◽  
pp. 495-502 ◽  
Author(s):  
T. I. Vitkina ◽  
T. P. Novgorodtseva ◽  
E. P. Kalinina ◽  
E. G. Lobanova ◽  
M. V. Antonyuk
Keyword(s):  
Immune Response ◽  
Management Strategies ◽  
Objective Evaluation ◽  
The Body ◽  
Immune Mechanisms ◽  
Persistent Inflammation ◽  
Th17 Lymphocytes ◽  
Group I ◽  
Asthma Patients

Despite a significant amount of works specifying immune mechanisms of bronchial asthma (BA), different phenotypes observed in this pathology need to be studied. The aim of present study was to analyze functional activity of Th1, Th2 и Th17 lymphocytes, and to determine features of inflammation in controlled and partly controlled asthma.We examined eighty-four BA patients that were divided into 2 groups, depending on the control of symptoms and the clinical course of BA. Group I included 45 patients with controlled BA, whereas group II included 39 patients with partially controlled asthma. The subsets of Th1, Th2, and Th17 lymphocytes were assessed by serum cytokine levels (TNFα, IFNγ, IL-2, IL-4, IL-6, IL-10, IL-17A) using flow cytometry technique.The results of this study were as follows: we have shown a combined T-helper (Th) immune response in asthma patients, with its origin depending on the degree of the disease control. Th2 (62%), Th1/Th2 (20%) and Th1 (18%) types of immune response have been detected in the patients with controlled BA. Th2/Th17 (49%), Th1/Th17 (13%) and Th17 (37%) types of immune response have been identified in the patients with partially controlled BA. It has been shown, that Th1 immune response in patients with controlled asthma is induced by intracellular infection. The formation of the Th1/Th2 phenotype is associated with a site of chronic bacterial infection revealed, and with persistence of viral infection in the body. This phenotype can be used as an indicator of asthma worsening. Further studies in the role of prevalent immune response type in the development of partially controlled BA have shown that activation of Th17 lymphocytes is associated with prolonged course of the disease. Irrespectively of initial phenotype, the development of Th17-dependent immune response seems to result from a durable systemic persistent inflammation.The views on the key role of Th1/Th2 balance in the development of asthma are accomplished by evidence of Th17 lymphocyte involvement into the process, and Th1/Th17, Th2/Th17 phenotypes seem to be the polar features of the disease. Estimation of intensity and phenotype of inflammation in BA will permit a more objective evaluation of the therapy applied, and to choose further management strategies.

scholarly journals Relationship Between Mucosal TNF-α Expression and Th1, Th17, Th22 and Treg Responses in Helicobacter Pylori Infection

2021 ◽  
Author(s):  
Ghorbanali Rahimian ◽  
Milad Shahini Shams Abadi ◽  
Reza Ahmadi ◽  
Mohammedhadi Shafigh ◽  
Fatemeh Azadegan-Dehkordi
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Treg Cells ◽  
Infected Group ◽  
Ulcer Disease ◽  
Tnf Α ◽  
H Pylori ◽  
Factor Α ◽  
Necrosis Factor

Abstract Background: Helicobacter pylori (H. pylori) -induced gastric inflammation in the gastric mucosa and significantly increases the risk of developing gastritis and peptic ulcer disease (PUD). The objective of this research is to determine the role of tumor necrosis factor-α (TNF-α) expression in the gastric mucosa of patients with H. pylori –associated gastritis and PUD compared to uninfected patients, and we determined the relation between TNF-α expression and Th1/Th17/Th22, and Treg cells.Methods: Fifty-five patients with H. pylori –associated gastritis, 47 patients with H. pylori –associated PUD, and 48 uninfected patients were in this research. Antrum biopsy was used to detect H. pylori, virulence factors and histopathological assessments.Results: Expression of TNF-α in the infected group was significantly higher than the uninfected group. Also, cagA/oipA-positive infected patients induce significantly more TNF-α expression than do cagA/oipA-negative infected patients. Expression of TNF-α was significantly increased in the PUD group than the gastritis group. Notably, TNF-α expression had a significant positive correlation with the frequency of Th1/Th17/Th22 lymphocytes in the PUD group.Conclusion: These findings indicate the importance of increasing TNF-α with Th1, Th17, Th22 responses increase as an important risk factor for PUD in context of H. pylori infection.

scholarly journals Production of Monocyte Chemoattractant Protein 1 in Tuberculosis Patients

1998 ◽  
Vol 66 (5) ◽  
pp. 2319-2322 ◽  
Author(s):  
YuanGuang Lin ◽  
JianHua Gong ◽  
Ming Zhang ◽  
Wanfen Xue ◽  
Peter F. Barnes
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Inflammatory Response ◽  
Lymph Nodes ◽  
Blood Monocytes ◽  
Monocyte Chemoattractant Protein 1 ◽  
Tuberculosis Patients ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein

ABSTRACT To investigate the role of monocyte chemoattractant protein 1 (MCP-1) in the immune response to Mycobacterium tuberculosis, we studied MCP-1 production in tuberculosis patients. CD14+ blood monocytes from tuberculosis patients spontaneously expressed higher levels of MCP-1 mRNA and protein than CD14+ monocytes from healthy tuberculin reactors. MCP-1 production in lymph nodes from tuberculosis patients was also markedly increased. These findings suggest that MCP-1 can contribute to the antimycobacterial inflammatory response by attracting monocytes and T lymphocytes.

scholarly journals Microbiomes other than the gut: inflammaging and age-related diseases

2020 ◽  
Vol 42 (5) ◽  
pp. 589-605 ◽  
Author(s):  
Aurelia Santoro ◽  
Jiangchao Zhao ◽  
Lu Wu ◽  
Ciriaco Carru ◽  
Elena Biagi ◽  
...  
Keyword(s):  
Immune System ◽  
Gut Microbiota ◽  
Homo Sapiens ◽  
Functional Integration ◽  
The Body ◽  
System Response ◽  
Mutual Adaptation ◽  
Age Related ◽  
Development And Aging

AbstractDuring the course of evolution, bacteria have developed an intimate relationship with humans colonizing specific body sites at the interface with the body exterior and invaginations such as nose, mouth, lung, gut, vagina, genito-urinary tract, and skin and thus constituting an integrated meta-organism. The final result has been a mutual adaptation and functional integration which confers significant advantages to humans and bacteria. The immune system of the host co-evolved with the microbiota to develop complex mechanisms to recognize and destroy invading microbes, while preserving its own bacteria. Composition and diversity of the microbiota change according to development and aging and contribute to humans’ health and fitness by modulating the immune system response and inflammaging and vice versa. In the last decades, we experienced an explosion of studies on the role of gut microbiota in aging, age-related diseases, and longevity; however, less reports are present on the role of the microbiota at different body sites. In this review, we describe the key steps of the co-evolution between Homo sapiens and microbiome and how this adaptation can impact on immunosenescence and inflammaging. We briefly summarized the role of gut microbiota in aging and longevity while bringing out the involvement of the other microbiota.

Plasmacytoid Dendritic Cells (PDC) and Th17 Immune Response Contribution in Skin Acute Graft-Versus-Host-Disease (GVHD)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4103-4103
Author(s):  
Florent Malard ◽  
Céline Bossard ◽  
Patrice Chevallier ◽  
Thierry Guillaume ◽  
Jacques Delaunay ◽  
...  
Keyword(s):  
Immune Response ◽  
Stem Cell ◽  
Autoimmune Diseases ◽  
Th17 Cells ◽  
Acute Gvhd ◽  
Unrelated Donor ◽  
Type I ◽  
Type I Ifn ◽  
Th17 Response

Abstract Abstract 4103 Background. Acute GVHD after allogeneic stem cell transplantation (allo-SCT) is an exaggerated immune response against alloantigens involving dysregulation of inflammatory cytokine cascades. Previous studies established an important role of Th1 cells in acute GVHD pathophysiology. However, the identification of proinflammatory Th17 cells which contribute to autoimmune diseases pathophysiology, raised the issue of the role of Th17 cells in human acute GVHD. Indeed, the contribution of Th17 cells in acute GVHD was assessed in GVHD mouse models with conflicting results. In addition, the role of the PDC subset (the professional type I IFN-secreting cells), which play an important role in triggering Th17-related cytokines and autoimmune diseases, is not yet established in the acute GVHD setting. This report investigated the role of Th17 cells and their interaction with PDC in cutaneous biopsies taken from patients with or without acute GVHD. Patients and Methods. Studies described in this report were performed in a single centre series of 38 patients who underwent allo-SCT for different hematological malignancies (n=37) and severe aplastic anemia (n=1). The median age of patients was 52 years (range, 17–70). The stem cell source was PBSCs in 27 cases (71%), CB in 6 cases and BM in 5 cases. 11 patients received transplant from a matched-related donor, and 27 patients from an unrelated donor. A reduced-intensity conditioning regimen was used in the majority of cases (n=29; 76%) Immunohistochemistry was performed on deparaffinized tissues sections using an indirect immunoperoxydase method. A quantitative evaluation of antigens expression was performed by counting the number of positive cells in the whole biopsy at 200 magnifications for each sample. Results. In this cohort, based on standard pathology criteria, 29 patients had a histologically proven skin acute GVHD. In all cases, biopsies were taken before initiation of systemic corticosteroid therapy. The remaining 9 patients did not have histological signs of acute GVHD (and did not develop clinical signs of acute GVHD) and thus, were used as controls. In order to identify the Th17 cell population, biopsies were tested for expression of the CD161 and CCR6 markers, and ROR-gamma-t, the key transcription factor that orchestrates the differentiation of Th17 cells. Significantly higher numbers of ROR-gamma-t+, CD161+ and CCR6+ cells were counted in the skin of patients with acute GVHD compared with intestinal mucosa of patients without acute GVHD, mainly found in the lamina propria but also in the epithelium of altered glands (p=0.001, p<0.0001 and p=0.01 for ROR-gamma-t, CD161 and CCR6 expression respectively).Given the role of PDCs in triggering Th17-related cytokines, we sought next to determine the proportion of PDCs in cutaneous biopsies from these same patients. This analysis showed a significant increase of BDCA2+ PDCs in the skin of patients with acute GVHD compared with skin of patients without acute GVHD (p=0.03). Moreover, we observed a strong expression of the type I IFN-inducible protein Mx1 in the skin of patients with acute GVHD compared with skin of patients without acute GVHD, reflecting the high production of type I IFN by the BDCA2+ PDCs. Conclusion. The current study shed some light on the role of Th17 cells in the context of cutaneous acute GVHD. Using well-established specific markers, we show that Th17 cells infiltrate skin biopsies from patients with acute GVHD. In addition, Th17 infiltration was paralleled by the infiltration of PDCs, suggesting a potential new pathophysiological link between PDCs and Th17 response in the context of cutaneous acute GVHD. This is consistent with studies showing that PDCs can drive the differentiation of Th17 cells. Functional analyses are currently ongoing. These data raise the prospect of future innovative approaches to optimize immunosuppression regimens for the treatment or prophylaxis of acute GVHD by targeting PDCs and the Th17 response. Disclosures: No relevant conflicts of interest to declare.

Role of monocyte chemoattractant protein-1, tumor necrosis factor-α and interleukin-6 in the control of malignant pleural effusion and survival in patients with primary lung adenocarcinoma

2012 ◽  
Vol 27 (2) ◽  
pp. 118-124 ◽  
Author(s):  
Qian Qian ◽  
Wen-Kui Sun ◽  
Ping Zhan ◽  
Yu Zhang ◽  
Yong Song ◽  
...  
Keyword(s):  
Pleural Effusion ◽  
Lung Adenocarcinoma ◽  
Malignant Pleural Effusion ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Primary Lung Adenocarcinoma ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

This study aimed at assessing the role of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the control of pleural effusion (PE) and survival in patients with primary lung adenocarcinoma. The concentrations of the 3 cytokines were measured in PE from 79 lung adenocarcinoma patients with malignant pleural effusion (MPE) and 23 patients with tuberculosis. Data were correlated with the efficacy of MPE control and patient survival. The level of MCP-1 in PE was significantly higher in patients with lung adenocarcinoma than those with tuberculosis. By contrast, the levels of TNF-α and IL-6 were significantly lower in patients with lung adenocarcinoma than those with tuberculosis. An MCP-1 level greater than 3,187 pg/mL (which was used as a cutoff point) indicated failure to control MPE (odds ratio [OR]=2.82, 95% confidence interval [CI]=1.02–7.82, p=0.04). In multivariate analysis, MCP-1 was confirmed as an independent prognostic factor for progression-free survival (hazard ratio [HR]=2.02, 95% CI=1.24–3.30, p=0.01). The level of MCP-1 in PE appears to be a reliable surrogate marker for evaluating the therapeutic efficacy in the control of MPE and predicting survival in lung adenocarcinoma patients with MPE.

3. Kill or be killed

2018 ◽  
pp. 24-32
Author(s):  
Dorothy H. Crawford
Keyword(s):  
Immune Response ◽  
Herpes Simplex ◽  
The Body ◽  
Protective Mechanism ◽  
Human Immune Response ◽  
Human Immune ◽  
Epstein Barr ◽  
Living Organisms ◽  
Simplex Virus

‘Kill or be killed’ shows how viruses survive—they must reproduce before the host either dies or its immune system recognizes and eliminates them. The transmission routes of viruses such as flu, measles, common cold, herpes simplex virus, HIV, Epstein–Barr, and hepatitis B are discussed. How do we fight viruses? All living organisms have defences against invading viruses. Vertebrates, and possibly some invertebrates, are immune to re-infection by the same virus. Another protective mechanism, used by plants, but also by insects and other animal species, is gene silencing by RNA interference. The human immune response is explained, discussing the role of lymphocytes and immunopathology, where the immune response may actually harm the body.

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