scholarly journals Reduction of IL-17A Might Suppress the Th1 Response and Promote the Th2 Response by Boosting the Function of Treg Cells during Silica-Induced Inflammatory ResponseIn Vitro

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Wen Tang ◽  
Fangwei Liu ◽  
Ying Chen ◽  
Laiyu Song ◽  
Wujing Dai ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Inflammatory Diseases ◽  
Treg Cells ◽  
Th2 Response ◽  
Th17 Response ◽  
Th1 Response ◽  
Different Types ◽  
Th17 Cytokine

Silica inhalation can induce chronic lung inflammation and fibrosis. Upon silica stimulation, activated macrophages trigger the T-lymphocyte which can differentiate into many different types of Th cells, including the recently discovered Th17 cells. IL-17A, the typical Th17 cytokine, is reported in some inflammatory diseases. However, the role of IL-17A in silica-induced inflammatory response is still not clear. The regulatory mechanism of silica-induced Th17 response also needs to be investigated. So we established a mice primary cell coculture system (macrophage and lymphocyte) to investigate the role of IL-17A in silica-induced inflammatory responsein vitro, by using anti-IL-17A mAb and IL-1Ra. Both anti-IL-17A mAb and IL-1Ra decreased the level of IL-17A and increased the function of Treg cells. The Th1 response was suppressed and the Th2 response was promoted by the addition of anti-IL-17A mAb or IL-1Ra. IL-1Ra treatment decreased the level of IL-6, whereas the levels of IL-23 and ROR-γt were increased. Our study demonstrated that IL-17A reduction altered the pattern of silica-induced Th responses by boosting the function of Treg cellsin vitro. Blocking the function of IL-1 signal pathway could suppress the level of IL-17A, which played the major role in modulating silica-induced Th responsesin vitro.

scholarly journals LncRNA H19 from T-Regulatory-Cell-Derived Exosomes Sponges miR-154-5p to Promote Osteogenic Differentiation of BMMSCs Through Upregulating POSTN

2021 ◽  
Author(s):  
Zhang Jing ◽  
Zhigang Li ◽  
Cuicui Liu ◽  
Yaxing Wu ◽  
Chenchen Li ◽  
...  
Keyword(s):  
T Cells ◽  
Osteogenic Differentiation ◽  
Bioinformatics Analysis ◽  
Inflammatory Diseases ◽  
Treg Cells ◽  
Fluorescent Labeling ◽  
T Regulatory Cell ◽  
New Type

Abstract Background: Mesenchymal stem cells (MSCs) can play an important role in anti-inflammatory function because it can induce Treg cells formation. Recent studies have confirmed that Tregs can release exosomes and induce immune tolerance as important immune cells. Thus, to clarify the function and regulatory mechanism of Treg cells-derived exosomes on osteogenic differentiation of BMMSCs is very important.Methods: CD4+ T cells isolated from mouse spleens were induced into CD4+ Foxp3+ Treg cells and co-cultured with BMMSCs. Then we isolated exosomes derived from Treg cells and tracked the exosomes using fluorescent labeling PKH67.Starbase, miRWalk, targetscan, bioinformatics analysis and functional complementation experiments to find relative lncRNA-miRNAs which involed in osteogenic differentiation of BMMSCs.Results: We found that exosomes derived from Tregs could enter BMMSCs and the expression of osteoblast-related genes were significantly up-regulated compared to the BMMSCs co-cultured with naïve T cells. LncRNA H19 from Tregs-derived exosomes could affect the osteogenic differentiation of BMMSCs in vitro by regulating POSTN expression via sponge miR-154-5p.Conclusions: This study demonstrated that important role of exosomes from Tregs in regulating osteogenic differentiation of BMMSCs. lncRNA H19 from Tregs-derived exosomes plays a positive regulatory role in osteogenic differentiation of BMMSCs through miR-154-5p/POSTN axis. It might has important clinical implications for inflammatory diseases and exosomes released from Tregs could be used as a new type of immunoregulation reagent for the treatment of periodontitis.

Interleukin-18 attracts plasmacytoid dendritic cells (DC2s) and promotes Th1 induction by DC2s through IL-18 receptor expression

Blood ◽  
2004 ◽  
Vol 103 (2) ◽  
pp. 648-655 ◽  
Author(s):  
Arthur Kaser ◽  
Susanne Kaser ◽  
Nicole C. Kaneider ◽  
Barbara Enrich ◽  
Christian J. Wiedermann ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Receptor Expression ◽  
Interleukin 18 ◽  
Th2 Response ◽  
Th1 Response ◽  
Initiation Phase ◽  
Helper Cell Type

Abstract In vivo evidence suggests that interleukin-18 (IL-18) shapes the development of adaptive immunity toward T-helper cell type 1 (Th1) responses. Monocyte-derived dendritic cells 1 (DC1s) preferentially induce a Th1 response, while plasmacytoid DC-derived DC2s have been linked to a Th2 response. We analyzed the role of IL-18 during the initiation phase of a Th response in vitro to elucidate the basis of these in vivo observations. IL-18 was constitutively released from DC1s, but not DC2s. Neutralization of IL-18 in coculture experiments of DC1s with allogeneic naive T lymphocytes did not alter the Th1/Th2 phenotype, while anti–IL-12 efficiently down-regulated the Th1 response. Unexpectedly, IL-18 receptor (IL-18R) α and β chains were expressed on DC2 lineage. IL-18R expression was functional, as IL-18 induced chemotaxis in plasmacytoid DCs (pre-DC2s) and enhanced the allostimulatory capacity of IL-3–differentiated DC2s. Pre-DC2s exposed to IL-18 skewed the development of Th cells toward Th1 in coculture experiments of DC2s and allogeneic naive T cells, which was inhibited by IL-12 p70 neutralization. IL-18 might have a profound role during the initiation phase of an immune response by recruiting pre-DC2s and modulating the function of DC2s.

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 MiR-22-3p suppresses sepsis-induced acute kidney injury by targeting PTEN

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Xudong Wang ◽  
Yali Wang ◽  
Mingjian Kong ◽  
Jianping Yang
Keyword(s):  
Acute Kidney Injury ◽  
Inflammatory Response ◽  
Periodic Acid ◽  
Kidney Injury ◽  
Luciferase Reporter ◽  
Tunel Staining ◽  
Tnf Α

Abstract Background: Septic acute kidney injury is considered as a severe and frequent complication that occurs during sepsis. The present study was performed to understand the role of miR-22-3p and its underlying mechanism in sepsis-induced acute kidney injury. Methods: Rats were injected with adenovirus carrying miR-22-3p or miR-NC in the caudal vein before cecal ligation. Meanwhile, HK-2 cells were transfected with the above adenovirus following LPS stimulation. We measured the markers of renal injury (blood urea nitrogen (BUN), serum creatinine (SCR)). Histological changes in kidney tissues were examined by hematoxylin and eosin (H&E), Masson staining, periodic acid Schiff staining and TUNEL staining. The levels of IL-1β, IL-6, TNF-α and NO were determined by ELISA assay. Using TargetScan prediction and luciferase reporter assay, we predicted and validated the association between PTEN and miR-22-3p. Results: Our data showed that miR-22-3p was significantly down-regulated in a rat model of sepsis-induced acute kidney injury, in vivo and LPS-induced sepsis model in HK-2 cells, in vitro. Overexpression of miR-22-3p remarkably suppressed the inflammatory response and apoptosis via down-regulating HMGB1, p-p65, TLR4 and pro-inflammatory factors (IL-1β, IL-6, TNF-α and NO), both in vivo and in vitro. Moreover, PTEN was identified as a target of miR-22-3p. Furthermore, PTEN knockdown augmented, while overexpression reversed the suppressive role of miR-22-3p in LPS-induced inflammatory response. Conclusions: Our results showed that miR-22-3p induced protective role in sepsis-induced acute kidney injury may rely on the repression of PTEN.

scholarly journals Autophagy and Age-Related Eye Diseases

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Xue Yang ◽  
Xinan Pan ◽  
Xiaorui Zhao ◽  
Jin Luo ◽  
Mingpu Xu ◽  
...  
Keyword(s):  
Eye Diseases ◽  
Regulatory Function ◽  
Ocular Diseases ◽  
Potential Therapeutic Target ◽  
Age Related ◽  
Different Types ◽  
Survival And Development ◽  
Catabolic Process

Background. Autophagy is a catabolic process that depends on the lysosome. It is usually used to maintain cellular homeostasis, survival and development by degrading abnormal substances and dysfunctional organelles, especially when the cell is exposed to starvation or other stresses. Increasing studies have reported that autophagy is associated with various eye diseases, of which aging is one of the important factors. Objective. To summarize the functional and regulatory role of autophagy in ocular diseases with aging, and discuss the possibility of autophagy-targeted therapy in age-related diseases. Methods. PubMed searches were performed to identify relevant articles published mostly in the last 5 years. The key words were used to retrieve including “autophagy”, “aging”, “oxidative stress AND autophagy”, “dry eye AND autophagy”, “corneal disease AND autophagy”, “glaucoma AND autophagy”, “cataract AND autophagy”, “AMD AND autophagy”, “cardiovascular diseases AND autophagy”, “diabetes AND autophagy”. After being classified and assessed, the most relevant full texts in English were chosen. Results. Apart from review articles, more than two research articles for each age-related eye diseases related to autophagy were retrieved. We only included the most relevant and recent studies for summary and discussion. Conclusion. Autophagy has both protective and detrimental effects on the progress of age-related eye diseases. Different types of studies based on certain situations in vitro showed distinct results, which do not necessarily coincide with the actual situation in human bodies completely. It means the exact role and regulatory function of autophagy in ocular diseases remains largely unknown. Although autophagy as a potential therapeutic target has been proposed, many problems still need to be solved before it applies to clinical practice.

scholarly journals High doses of immunoglobulin G attenuate immune aggregate-mediated complement activation by enhancing physiologic cleavage of C3b in C3bn- IgG complexes

Blood ◽  
1996 ◽  
Vol 88 (1) ◽  
pp. 184-193 ◽  
Author(s):  
HU Lutz ◽  
P Stammler ◽  
E Jelezarova ◽  
M Nater ◽  
PJ Spath
Keyword(s):  
Inflammatory Diseases ◽  
Factor H ◽  
Human Igg ◽  
Partial Protection ◽  
Beneficial Effects ◽  
High Concentrations ◽  
High Doses ◽  
Immune Aggregates

Abstract Intravenously applied human IgG has beneficial effects in treating inflammatory diseases, presumably because it has a complement attenuating role. This role of IgG was studied in vitro by following C3 activation and inactivation in sera that were supplemented with exogenous human IgG and incubated with immune aggregates. IgG added at 2 to 10 mg/mL stimulated the physiologic inactivation of C3b-containing complexes twofold to threefold in 20% sera. This, in turn, lowered the overall C3 activation by 28%, as new C3 convertases primarily assembled on C3b-containing complexes. Exogenous IgG (5 mg/mL) also stimulated inactivation of purified C3b2-IgG complexes, whereby their half-life dropped from 3–4 to 1.5 minutes in 20% serum. IgG appeared to act like a modulator of factor H and I because it did not stimulate inactivation of C3b-containing complexes in factor I-deficient serum. Thus, the known partial protection of C3bn-IgG complexes from inactivation by factor H and I was downregulated by high concentrations of IgG. The ability of high doses of IgG to stimulate complement inactivation is a novel regulatory role of IgG. This may be one of the molecular principles for its therapeutic efficacy in treating complement-mediated inflammations.

scholarly journals Interleukin 4 induces cultured monocytes/macrophages to form giant multinucleated cells.

1988 ◽  
Vol 167 (2) ◽  
pp. 598-611 ◽  
Author(s):  
A McInnes ◽  
D M Rennick
Keyword(s):  
Bone Marrow ◽  
Inflammatory Response ◽  
Cell Fusion ◽  
Cell Cultures ◽  
Soft Agar ◽  
Interleukin 4 ◽  
Multinucleated Cells ◽  
Granulomatous Lesions

Giant multinucleated cells (GMCs) are associated with granulomatous lesions that form in response to various infectious and noninfectious agents. The present study shows that mouse IL-4 induces the in vitro formation of GMCs by factor-dependent bone marrow and alveolar monocytes via cell fusion. GMCs appear 2 d after incubation of cell cultures with 20 U/ml or more of IL-4. Anti-IL-4 mAbs block the appearance of GMCs in these cultures, indicating that IL-4 acts directly on monocytes to promote fusion and does not secondarily induce the production of other soluble fusion factors. In soft agar cultures, IL-4 also causes the aggregation of macrophages and diminishes their migration. The role of IL-4 in a granulomatous inflammatory response is discussed.

scholarly journals Pivotal role of M-DC8+ monocytes from viremic HIV-infected patients in TNFα overproduction in response to microbial products

Blood ◽  
2012 ◽  
Vol 120 (11) ◽  
pp. 2259-2268 ◽  
Author(s):  
Charles-Antoine Dutertre ◽  
Sonia Amraoui ◽  
Annalisa DeRosa ◽  
Jean-Pierre Jourdain ◽  
Lene Vimeux ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Hiv Infection ◽  
Mononuclear Cells ◽  
Inflammatory Diseases ◽  
Intestinal Epithelial ◽  
Color Flow ◽  
Gm Csf ◽  
Cell Counts

Abstract HIV infects activated CD4+ T cells and induces their depletion. Progressive HIV infection leading to AIDS is fueled by chronic immune hyperactivation, mediated by inflammatory cytokines like TNFα. This has been related to intestinal epithelial damage and microbial LPS translocation into the circulation. Using 11-color flow cytometry, cell sorting, and cell culture, we investigated the numbers and TNFα production of fully defined circulating dendritic cell and monocyte populations during HIV-1 infection. In 15 viremic, untreated patients, compared with 8 treated, virologically suppressed patients or to 13 healthy blood donors, circulating CD141 (BDCA-3)+ and CD1c (BDCA-1)+ dendritic cell counts were reduced. Conversely, CD14+CD16++ monocyte counts were increased, particularly those expressing M-DC8, while classical CD14++CD16−M-DC8− monocyte numbers were unchanged. Blood mononuclear cells from viremic patients produced more TNFα in response to LPS than those from virologically suppressed patients. M-DC8+ monocytes were mostly responsible for this overproduction. Moreover, M-DC8+ monocytes differentiated in vitro from classical monocytes using M-CSF and GM-CSF, which is increased in viremic patient's plasma. This M-DC8+ monocyte population, which is involved in the pathogenesis of chronic inflammatory diseases like Crohn disease, might thus be considered as a major actor in the immune hyperactivation fueling HIV infection progression.

scholarly journals Context-Dependent Effect of Glucocorticoids on the Proliferation, Differentiation, and Apoptosis of Regulatory T Cells: A Review of the Empirical Evidence and Clinical Applications

2019 ◽  
Vol 20 (5) ◽  
pp. 1142 ◽  
Author(s):  
Luigi Cari ◽  
Francesca De Rosa ◽  
Giuseppe Nocentini ◽  
Carlo Riccardi
Keyword(s):  
T Cells ◽  
Treg Cell ◽  
Inflammatory Diseases ◽  
Treg Cells ◽  
Cell Number ◽  
Lymphoid Tissues ◽  
Treg Number ◽  
Context Dependent

Glucocorticoids (GCs) are widely used to treat several diseases because of their powerful anti-inflammatory and immunomodulatory effects on immune cells and non-lymphoid tissues. The effects of GCs on T cells are the most relevant in this regard. In this review, we analyze how GCs modulate the survival, maturation, and differentiation of regulatory T (Treg) cell subsets into both murine models and humans. In this way, GCs change the Treg cell number with an impact on the mid-term and long-term efficacy of GC treatment. In vitro studies suggest that the GC-dependent expansion of Treg cells is relevant when they are activated. In agreement with this observation, the GC treatment of patients with established autoimmune, allergic, or (auto)inflammatory diseases causes an expansion of Treg cells. An exception to this appears to be the local GC treatment of psoriatic lesions. Moreover, the effects on Treg number in patients with multiple sclerosis are uncertain. The effects of GCs on Treg cell number in healthy/diseased subjects treated with or exposed to allergens/antigens appear to be context-dependent. Considering the relevance of this effect in the maturation of the immune system (tolerogenic response to antigens), the success of vaccination (including desensitization), and the tolerance to xenografts, the findings must be considered when planning GC treatment.

scholarly journals LPS-Treated Podocytes Polarize Naive CD4+ T Cells into Th17 and Treg Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Da-Hai Yuan ◽  
Yang Jia ◽  
Omar Mohamud Hassan ◽  
Li-Yun Xu ◽  
Xiao-Chuan Wu
Keyword(s):  
T Cells ◽  
Th17 Cells ◽  
Treg Cells ◽  
Mouse Bone Marrow ◽  
Th17 Response ◽  
Mhc Ii ◽  
Histocompatibility Complex ◽  
Th 17 ◽  
Induction Process

Aim. Our study is aimed at investigating whether Lipopolysaccharide- (LPS-) treated podocytes could polarize naive CD4+ T cells into different subsets in vitro. Materials and Methods. Podocytes and mouse bone marrow-derived dendritic cells (BMDCs) were first cultured with 25 μg/ml LPS for 6 hours, respectively. Then, naive CD4+ T cells were cocultured with the LPS-treated podocytes or BMDCs at a ratio of 1 : 1 or 1 : 1 : 1. After 48 hours, we collected the suspended cells and supernatant from all groups to measure T helper (Th)17 cells, regulatory T (Treg) cells, and cytokine concentration. Results. We observed the expression of CD80 and major histocompatibility complex class II molecule (MHC II) in podocytes but did not found the upregulation of them after treating podocytes with LPS. LPS-treated podocytes could induce naive CD4+ T cells to Th17 cells and Treg cells with a higher ratio of Th17/Treg than BMDCs. Possible interaction between podocytes and BMDCs may exist in the induction process of Th17 cells and Treg cells. Conclusion. Our study proved that CD80 and MHC II were constitutively expressed in podocytes but not upregulated by LPS. LPS-treated podocytes could polarize naive CD4+ T cells into Th17 and Treg cells and affect the Th17/Treg balance and may incline to cause a Th17 response.

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