Human rhinovirus recognition in non-immune cells is mediated byToll-like receptors and MDA-5, which trigger a synergetic pro-inflammatory immune response

G protein-coupled receptor kinase 2 (GRK2), as a vital Ser/Thr kinase, is an important regulatory protein in the inflammatory immune response (IIR) by maintaining the balance between the function of inflammatory immune cells and non-conventional inflammatory immune cells and regulating inflammatory immune cell infiltration, inflammatory cytokine secretion, and the signaling associated with endothelial function. However, the imbalance of GRK2 expression and activity plays an important role in the development of IIR-related diseases, such as hypertension, heart failure, Alzheimer’s disease, type 2 diabetes mellitus, insulin resistance, rheumatoid arthritis, thyroid cancer, multiple sclerosis, and liver cancer. Small molecule GRK2 inhibitors, including balanol, Takeda inhibitors, paroxetine and derivatives, M119 and gallein, peptides, RNA aptamers, Raf kinase inhibitory protein, and microRNAs, that can directly inhibit GRK2 kinase activity have been identified by different strategies. This review discusses recent progress in one of the hallmark molecular abnormalities of GRK2 in IIR-related diseases and explores the soft regulation of IIR by innovative drugs reducing the excessive activity of GRK2 to basal levels, without damaging normal physiological function, to ameliorate inflammatory disorders.

Download Full-text

Day‐7 embryos generate an anti‐inflammatory immune response in peripheral blood immune cells in superovulated cows

American Journal of Reproductive Immunology ◽

10.1111/aji.13069 ◽

2018 ◽

Vol 81 (2) ◽

pp. e13069 ◽

Cited By ~ 1

Author(s):

Anup K. Talukder ◽

Mohammad B. Rashid ◽

Toshiro Takedomi ◽

Satoru Moriyasu ◽

Kazuhiko Imakawa ◽

...

Keyword(s):

Immune Response ◽

Immune Cells ◽

Peripheral Blood ◽

Inflammatory Immune Response ◽

Anti Inflammatory

Download Full-text

The alarmin IL-33 drives a ST2+ Treg-mediated anti-inflammatory immune response during immune-mediated hepatitis

10.1055/s-0038-1677273 ◽

2019 ◽

Author(s):

K Neumann ◽

F Heinrich ◽

A Ochel ◽

G Tiegs

Keyword(s):

Immune Response ◽

Immune Mediated ◽

Inflammatory Immune Response ◽

Anti Inflammatory

Download Full-text

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

Journal of Neuroinflammation ◽

10.1186/s12974-020-02057-z ◽

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.

Download Full-text

Pattern of inflammatory immune response determines the clinical course and outcome of COVID-19: unbiased clustering analysis

Scientific Reports ◽

10.1038/s41598-021-87668-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Eunyoung Emily Lee ◽

Kyoung-Ho Song ◽

Woochang Hwang ◽

Sin Young Ham ◽

Hyeonju Jeong ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Clustering Analysis ◽

Validation Cohort ◽

Inflammatory Responses ◽

Clinical Course ◽

Severe Disease ◽

Outcome Data ◽

Inflammatory Immune Response ◽

Cluster 2

AbstractThe objective of the study was to identify distinct patterns in inflammatory immune responses of COVID-19 patients and to investigate their association with clinical course and outcome. Data from hospitalized COVID-19 patients were retrieved from electronic medical record. Supervised k-means clustering of serial C-reactive protein levels (CRP), absolute neutrophil counts (ANC), and absolute lymphocyte counts (ALC) was used to assign immune responses to one of three groups. Then, relationships between patterns of inflammatory responses and clinical course and outcome of COVID-19 were assessed in a discovery and validation cohort. Unbiased clustering analysis grouped 105 patients of a discovery cohort into three distinct clusters. Cluster 1 (hyper-inflammatory immune response) was characterized by high CRP levels, high ANC, and low ALC, whereas Cluster 3 (hypo-inflammatory immune response) was associated with low CRP levels and normal ANC and ALC. Cluster 2 showed an intermediate pattern. All patients in Cluster 1 required oxygen support whilst 61% patients in Cluster 2 and no patient in Cluster 3 required supplementary oxygen. Two (13.3%) patients in Cluster 1 died, whereas no patient in Clusters 2 and 3 died. The results were confirmed in an independent validation cohort of 116 patients. We identified three different patterns of inflammatory immune response to COVID-19. Hyper-inflammatory immune responses with elevated CRP, neutrophilia, and lymphopenia are associated with a severe disease and a worse outcome. Therefore, targeting the hyper-inflammatory response might improve the clinical outcome of COVID-19.

Download Full-text

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

Viruses ◽

10.3390/v13030514 ◽

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.

Download Full-text

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

Biology ◽

10.3390/biology10020070 ◽

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.

Download Full-text

Polymerized albumin restores impaired hemodynamics in endotoxemia and polymicrobial sepsis

Scientific Reports ◽

10.1038/s41598-021-90431-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Donald A. Belcher ◽

Alexander T. Williams ◽

Andre F. Palmer ◽

Pedro Cabrales

Keyword(s):

Septic Shock ◽

Immune Response ◽

Fluid Resuscitation ◽

Cecal Ligation ◽

Vascular Wall ◽

Polymicrobial Sepsis ◽

Vascular Integrity ◽

Fluid Extravasation ◽

Inflammatory Immune Response ◽

Polymerized Human Serum Albumin

AbstractFluid resuscitation following severe inflammation-induced hypoperfusion is critical for the restoration of hemodynamics and the prevention of multiorgan dysfunction syndrome during septic shock. Fluid resuscitation with commercially available crystalloid and colloid solutions only provides transient benefits, followed by fluid extravasation and tissue edema through the inflamed endothelium. The increased molecular weight (M.W.) of polymerized human serum albumin (PolyHSA) can limit fluid extravasation, leading to restoration of hemodynamics. In this prospective study, we evaluated how fluid resuscitation with PolyHSA impacts the hemodynamic and immune response in a lipopolysaccharide (LPS) induced endotoxemia mouse model. Additionally, we evaluated fluid resuscitation with PolyHSA in a model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Resuscitation with PolyHSA attenuated the immune response and improved the maintenance of systemic hemodynamics and restoration of microcirculatory hemodynamics. This decrease in inflammatory immune response and maintenance of vascular wall shear stress likely contributes to the maintenance of vascular integrity following fluid resuscitation with PolyHSA. The sustained restoration of perfusion, decrease in pro-inflammatory immune response, and improved vascular integrity that results from the high M.W. of PolyHSA indicates that a PolyHSA based solution is a potential resuscitation fluid for endotoxic and septic shock.

Download Full-text

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

Scientific Reports ◽

10.1038/s41598-020-80291-4 ◽

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.

Download Full-text

Quantitative Methodologies to Dissect Immune Cell Mechanobiology

Cells ◽

10.3390/cells10040851 ◽

2021 ◽

Vol 10 (4) ◽

pp. 851

Author(s):

Veronika Pfannenstill ◽

Aurélien Barbotin ◽

Huw Colin-York ◽

Marco Fritzsche

Keyword(s):

Mechanical Properties ◽

Immune Response ◽

Time Scales ◽

Immune Cells ◽

Cell Mechanics ◽

Immune Cell ◽

Biological Significance ◽

Force Generation ◽

Tissue Microenvironment ◽

And Behavior

Mechanobiology seeks to understand how cells integrate their biomechanics into their function and behavior. Unravelling the mechanisms underlying these mechanobiological processes is particularly important for immune cells in the context of the dynamic and complex tissue microenvironment. However, it remains largely unknown how cellular mechanical force generation and mechanical properties are regulated and integrated by immune cells, primarily due to a profound lack of technologies with sufficient sensitivity to quantify immune cell mechanics. In this review, we discuss the biological significance of mechanics for immune cells across length and time scales, and highlight several experimental methodologies for quantifying the mechanics of immune cells. Finally, we discuss the importance of quantifying the appropriate mechanical readout to accelerate insights into the mechanobiology of the immune response.

Download Full-text