scholarly journals The Intensity of Radiotherapy-Elicited Immune Response Is Associated with Esophageal Cancer Clearance

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Jin-lu Ma ◽  
Long Jin ◽  
Yao-Dong Li ◽  
Chen-chen He ◽  
Xi-jing Guo ◽  
...  
Keyword(s):  
Immune Response ◽  
Dna Damage ◽  
Esophageal Cancer ◽  
Immune Cells ◽  
Interleukin 2 ◽  
Therapeutic Interventions ◽  
Hematologic Toxicity ◽  
Serum Concentrations ◽  
Local Response ◽  
Therapeutic Modalities

Radiation therapy is one of the standard therapeutic modalities for esophageal cancer, achieving its main antitumor efficacy through DNA damage. However, accumulating evidence shows that radiotherapy can substantially alter the tumor microenvironment, particularly with respect to its effects on immune cells. We hypothesized that the immune response elicited by radiotherapy may be as important as the radiation itself for successful treatment. More specifically, immunomodulatory cytokines may enhance the effectiveness of radiotherapy. To investigate this hypothesis, we measured changes in the serum interferon-gamma (IFN-γ) and interleukin-2 (IL-2) concentrations during radiotherapy and compared these modifications with outcomes. We found that serum concentrations of IL-2 and IFN-γwere positively associated with local response to radiotherapy in esophageal cancer. More generally, the intensity of the radiotherapy-elicited immune response was positively associated with local response to radiotherapy in esophageal cancer. Changes in serum IL-2 and IFN-γconcentrations were further associated with increased risks of acute hematologic toxicity and acute organ toxicity of the esophagus, lung, and skin. These results suggest that deciphering the mechanisms of radiotherapy-elicited immune response may help in the development of therapeutic interventions that would enhance the efficacy of radiotherapy and convert some ineffective responses to effective responses.

scholarly journals Dynamics of Dual Specificity Phosphatases and Their Interplay with Protein Kinases in Immune Signaling

2019 ◽  
Vol 20 (9) ◽  
pp. 2086 ◽  
Author(s):  
Yashwanth Subbannayya ◽  
Sneha M. Pinto ◽  
Korbinian Bösl ◽  
T. S. Keshava Prasad ◽  
Richard K. Kandasamy
Keyword(s):  
Immune Response ◽  
Protein Kinases ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Tlr4 Signaling ◽  
Cyclin Dependent Kinases ◽  
Therapeutic Modalities ◽  
Dual Specificity ◽  
Mitogen Activated Protein ◽  
Dual Specificity Phosphatases

Dual specificity phosphatases (DUSPs) have a well-known role as regulators of the immune response through the modulation of mitogen-activated protein kinases (MAPKs). Yet the precise interplay between the various members of the DUSP family with protein kinases is not well understood. Recent multi-omics studies characterizing the transcriptomes and proteomes of immune cells have provided snapshots of molecular mechanisms underlying innate immune response in unprecedented detail. In this study, we focus on deciphering the interplay between members of the DUSP family with protein kinases in immune cells using publicly available omics datasets. Our analysis resulted in the identification of potential DUSP-mediated hub proteins including MAPK7, MAPK8, AURKA, and IGF1R. Furthermore, we analyzed the association of DUSP expression with TLR4 signaling and identified VEGF, FGFR, and SCF-KIT pathway modules to be regulated by the activation of TLR4 signaling. Finally, we identified several important kinases including LRRK2, MAPK8, and cyclin-dependent kinases as potential DUSP-mediated hubs in TLR4 signaling. The findings from this study have the potential to aid in the understanding of DUSP signaling in the context of innate immunity. Further, this will promote the development of therapeutic modalities for disorders with aberrant DUSP signaling.

scholarly journals Dynamics of dual specificity phosphatases and their interplay with protein kinases in immune signaling

2019 ◽  
Author(s):  
Yashwanth Subbannayya ◽  
Sneha M. Pinto ◽  
Korbinian Bösl ◽  
T. S. Keshava Prasad ◽  
Richard K. Kandasamy
Keyword(s):  
Immune Response ◽  
Protein Kinases ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Tlr4 Signaling ◽  
Cyclin Dependent Kinases ◽  
Therapeutic Modalities ◽  
Dual Specificity ◽  
Mitogen Activated Protein ◽  
Dual Specificity Phosphatases

AbstractDual specificity phosphatases (DUSPs) have a well-known role as regulators of the immune response through the modulation of mitogen activated protein kinases (MAPKs). Yet the precise interplay between the various members of the DUSP family with protein kinases is not well understood. Recent multi-omics studies characterizing the transcriptomes and proteomes of immune cells have provided snapshots of molecular mechanisms underlying innate immune response in unprecedented detail. In this study, we focused on deciphering the interplay between members of the DUSP family with protein kinases in immune cells using publicly available omics datasets. Our analysis resulted in the identification of potential DUSP-mediated hub proteins including MAPK7, MAPK8, AURKA, and IGF1R. Furthermore, we analyzed the association of DUSP expression with TLR4 signaling and identified VEGF, FGFR and SCF-KIT pathway modules to be regulated by the activation of TLR4 signaling. Finally, we identified several important kinases including LRRK2, MAPK8, and cyclin-dependent kinases as potential DUSP-mediated hubs in TLR4 signaling. The findings from this study has the potential to aid in the understanding of DUSP signaling in the context of innate immunity. Further, this will promote the development of therapeutic modalities for disorders with aberrant DUSP signaling.

scholarly journals The immune response of T cells and therapeutic targets related to regulating the levels of T helper cells after ischaemic stroke

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Tian-Yu Lei ◽  
Ying-Ze Ye ◽  
Xi-Qun Zhu ◽  
Daniel Smerin ◽  
Li-Juan Gu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Ischaemic Stroke ◽  
Immune Cells ◽  
Tissue Injury ◽  
Recovery Period ◽  
Vital Functions ◽  
Anti Inflammatory

AbstractThrough considerable effort in research and clinical studies, the immune system has been identified as a participant in the onset and progression of brain injury after ischaemic stroke. Due to the involvement of all types of immune cells, the roles of the immune system in stroke pathology and associated effects are complicated. Past research concentrated on the functions of monocytes and neutrophils in the pathogenesis of ischaemic stroke and tried to demonstrate the mechanisms of tissue injury and protection involving these immune cells. Within the past several years, an increasing number of studies have elucidated the vital functions of T cells in the innate and adaptive immune responses in both the acute and chronic phases of ischaemic stroke. Recently, the phenotypes of T cells with proinflammatory or anti-inflammatory function have been demonstrated in detail. T cells with distinctive phenotypes can also influence cerebral inflammation through various pathways, such as regulating the immune response, interacting with brain-resident immune cells and modulating neurogenesis and angiogenesis during different phases following stroke. In view of the limited treatment options available following stroke other than tissue plasminogen activator therapy, understanding the function of immune responses, especially T cell responses, in the post-stroke recovery period can provide a new therapeutic direction. Here, we discuss the different functions and temporal evolution of T cells with different phenotypes during the acute and chronic phases of ischaemic stroke. We suggest that modulating the balance between the proinflammatory and anti-inflammatory functions of T cells with distinct phenotypes may become a potential therapeutic approach that reduces the mortality and improves the functional outcomes and prognosis of patients suffering from ischaemic stroke.

scholarly journals SARS-CoV-2 RNA and antibodies in tear fluid

2021 ◽  
Vol 6 (1) ◽  
pp. e000733
Author(s):  
Astrid Muyldermans ◽  
Maria Bjerke ◽  
Thomas Demuyser ◽  
Deborah De Geyter ◽  
Ingrid Wybo ◽  
...  
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Spike Protein ◽  
Tear Fluid ◽  
Local Response ◽  
Schirmer Test ◽  
Humoral Immune ◽  
Non Invasive ◽  
Reverse Transcription Pcr ◽  
Ocular Symptoms

Background/aimsSARS-CoV-2 is highly contagious. More evidence concerning extrapulmonary transmission routes such as the eyes is urgently needed. Although the humoral immune response is important in the viral containment, the local response in tears has not yet been studied. The aim of our study was twofold: to assess the prevalence of both SARS-CoV-2 RNA and antibodies in tear fluid.MethodsIn a first series, nasopharyngeal sampling and tear sampling by Schirmer test strips were performed in 26 acutely ill patients with COVID-19 to assess the presence of SARS-CoV-2 RNA by reverse transcription PCR. In a second series, IgG and IgA responses to SARS-CoV-2 spike protein in serum and tear fluid of convalescent individuals (n=22) were compared with control individuals (n=15) by ELISA.ResultsSARS-CoV-2 RNA was detected in tears of 7/26 (26.9%) patients with COVID-19. None of them had ocular symptoms. Convalescent individuals displayed a significant higher ratio of IgG (p<0.0001) and IgA (p=0.0068) in tears compared with control individuals. A sensitivity of 77.3% and specificity of 93.3% was observed for IgG, and 59.1% and 100% for IgA.ConclusionsOur results demonstrate the presence of SARS-CoV-2 RNA and a local IgG and IgA immune response in tear fluid. These data confirm the possibility of SARS-CoV-2 transmission through tear fluid and the importance of the eye as a first defence against SARS-CoV-2, indicating the potential of tears as a non-invasive surrogate for serum in monitoring the host immune response.

scholarly journals Profiles of Peripheral Immune Cells of Uncomplicated COVID-19 Cases with Distinct Viral RNA Shedding Periods

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 514
Author(s):  
Denise Utami Putri ◽  
Cheng-Hui Wang ◽  
Po-Chun Tseng ◽  
Wen-Sen Lee ◽  
Fu-Lun Chen ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Cells ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Severe Disease ◽  
Viral Rna ◽  
Disease Course ◽  
Peripheral Blood Mononuclear ◽  
Peripheral Immune Cells ◽  
Cell Profile

The heterogeneity of immune response to COVID-19 has been reported to correlate with disease severity and prognosis. While so, how the immune response progress along the period of viral RNA-shedding (VRS), which determines the infectiousness of disease, is yet to be elucidated. We aim to exhaustively evaluate the peripheral immune cells to expose the interplay of the immune system in uncomplicated COVID-19 cases with different VRS periods and dynamic changes of the immune cell profile in the prolonged cases. We prospectively recruited four uncomplicated COVID-19 patients and four healthy controls (HCs) and evaluated the immune cell profile throughout the disease course. Peripheral blood mononuclear cells (PBMCs) were collected and submitted to a multi-panel flowcytometric assay. CD19+-B cells were upregulated, while CD4, CD8, and NK cells were downregulated in prolonged VRS patients. Additionally, the pro-inflammatory-Th1 population showed downregulation, followed by improvement along the disease course, while the immunoregulatory cells showed upregulation with subsequent decline. COVID-19 patients with longer VRS expressed an immune profile comparable to those with severe disease, although they remained clinically stable. Further studies of immune signature in a larger cohort are warranted.

scholarly journals RhoA- and Actin-Dependent Functions of Macrophages from the Rodent Cardiac Transplantation Model Perspective -Timing Is the Essence

Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 70
Author(s):  
Malgorzata Kloc ◽  
Ahmed Uosef ◽  
Martha Villagran ◽  
Robert Zdanowski ◽  
Jacek Z. Kubiak ◽  
...  
Keyword(s):  
Immune Response ◽  
Circadian Rhythm ◽  
Immune Cells ◽  
Chronic Rejection ◽  
Cardiac Transplantation ◽  
Small Gtpase ◽  
Eukaryotic Cells ◽  
Transplantation Model

The small GTPase RhoA, and its down-stream effector ROCK kinase, and the interacting Rac1 and mTORC2 pathways, are the principal regulators of the actin cytoskeleton and actin-related functions in all eukaryotic cells, including the immune cells. As such, they also regulate the phenotypes and functions of macrophages in the immune response and beyond. Here, we review the results of our and other’s studies on the role of the actin and RhoA pathway in shaping the macrophage functions in general and macrophage immune response during the development of chronic (long term) rejection of allografts in the rodent cardiac transplantation model. We focus on the importance of timing of the macrophage functions in chronic rejection and how the circadian rhythm may affect the anti-chronic rejection therapies.

scholarly journals LncRNA HOTAIR regulates glucose transporter Glut1 expression and glucose uptake in macrophages during inflammation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Monira Obaid ◽  
S. M. Nashir Udden ◽  
Prasanna Alluri ◽  
Subhrangsu S. Mandal
Keyword(s):  
Immune Response ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Immune Cells ◽  
Glucose Transporter ◽  
Energy Needs ◽  
Glut1 Expression ◽  
Lncrna Hotair ◽  
Upstream Regulators ◽  
Glucose Transporter Glut1

AbstractInflammation plays central roles in the immune response. Inflammatory response normally requires higher energy and therefore is associated with glucose metabolism. Our recent study demonstrates that lncRNA HOTAIR plays key roles in NF-kB activation, cytokine expression, and inflammation. Here, we investigated if HOTAIR plays any role in the regulation of glucose metabolism in immune cells during inflammation. Our results demonstrate that LPS-induced inflammation induces the expression of glucose transporter isoform 1 (Glut1) which controls the glucose uptake in macrophages. LPS-induced Glut1 expression is regulated via NF-kB activation. Importantly, siRNA-mediated knockdown of HOTAIR suppressed the LPS-induced expression of Glut1 suggesting key roles of HOTAIR in LPS-induced Glut1 expression in macrophage. HOTAIR induces NF-kB activation, which in turn increases Glut1 expression in response to LPS. We also found that HOTAIR regulates glucose uptake in macrophages during LPS-induced inflammation and its knockdown decreases LPS-induced increased glucose uptake. HOTAIR also regulates other upstream regulators of glucose metabolism such as PTEN and HIF1α, suggesting its multimodal functions in glucose metabolism. Overall, our study demonstrated that lncRNA HOTAIR plays key roles in LPS-induced Glut1 expression and glucose uptake by activating NF-kB and hence HOTAIR regulates metabolic programming in immune cells potentially to meet the energy needs during the immune response.

scholarly journals Diverse immune response of DNA damage repair-deficient tumors

2021 ◽  
Vol 2 (5) ◽  
pp. 100276
Author(s):  
Tao Qing ◽  
Tomi Jun ◽  
Katherine E. Lindblad ◽  
Amaia Lujambio ◽  
Michal Marczyk ◽  
...  
Keyword(s):  
Immune Response ◽  
Dna Damage ◽  
Dna Damage Repair ◽  
Damage Repair
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