scholarly journals Signals and Mechanisms Regulating Monocyte and Macrophage Activation in the Pathogenesis of Juvenile Idiopathic Arthritis

2021 ◽  
Vol 22 (15) ◽  
pp. 7960
Author(s):  
Chao-Yi Wu ◽  
Huang-Yu Yang ◽  
Jing-Long Huang ◽  
Jenn-Haung Lai
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Innate Immune System ◽  
Tissue Repair ◽  
Macrophage Activation ◽  
Cell Activation ◽  
Innate Immune ◽  
Inflammatory Joint Diseases ◽  
Tissue Repair And Regeneration ◽  
Related Cell ◽  
Key Players

Monocytes (Mos) and macrophages (Mφs) are key players in the innate immune system and are critical in coordinating the initiation, expansion, and regression of many autoimmune diseases. In addition, they display immunoregulatory effects that impact inflammation and are essential in tissue repair and regeneration. Juvenile idiopathic arthritis (JIA) is an umbrella term describing inflammatory joint diseases in children. Accumulated evidence suggests a link between Mo and Mφ activation and JIA pathogenesis. Accordingly, topics regarding the signals and mechanisms regulating Mo and Mφ activation leading to pathologies in patients with JIA are of great interest. In this review, we critically summarize recent advances in the understanding of how Mo and Mφ activation is involved in JIA pathogenesis and focus on the signaling pathways and mechanisms participating in the related cell activation processes.

scholarly journals Neutrophils and NETs in modulating acute and chronic inflammation

Blood ◽  
2019 ◽  
Vol 133 (20) ◽  
pp. 2178-2185 ◽  
Author(s):  
Fernanda V. S. Castanheira ◽  
Paul Kubes
Keyword(s):  
Chronic Inflammation ◽  
Host Defense ◽  
Innate Immune System ◽  
Tissue Repair ◽  
Essential Role ◽  
Neutrophil Extracellular Traps ◽  
Innate Immune ◽  
Extracellular Traps ◽  
Acute And Chronic Inflammation

Abstract Neutrophils are an absolutely essential part of the innate immune system, playing an essential role in the control of infectious diseases but more recently are also being viewed as important players in tissue repair. Neutrophils are able to counteract an infection through phagocytosis and/or the release of neutrophil extracellular traps (NETs). By contrast, neutrophils help repair damaged tissues, limiting NET production but still phagocytosing debris. However, when inflammation is recurrent, or the inciting agent persists, neutrophils through a frustrated inability to resolve the problem can release NETs to exacerbate tissue damage during inappropriate inflammation. In this review, we discuss the mechanisms of NET formation, as well as the apparent paradoxical role of neutrophils and NETs in host defense, chronic inflammation, and tissue disrepair.

216 Anti-tumor activity of iosH2 by blocking LILRB2 receptor signalling

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A235-A235
Author(s):  
Osiris Marroquin Belaunzaran ◽  
Anahita Rafiei ◽  
Anil Kumar ◽  
Julia Kolibaba ◽  
Lorenz Vogt ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Innate Immune System ◽  
Cell Activation ◽  
Innate Immune ◽  
High Affinity ◽  
Anti Tumor Activity

BackgroundThe human leukocyte immunoglobulin-like receptor family B (LILR B) acts as check point blockade of the innate immune system by inhibiting leukocyte activation through SHP phosphatase recruitment. Some of the physiological ligands include classical HLA class I molecules, including beta-2-microglobulin (B2M) free open conformers (OC). Natural HLA-OC expression is known from autoimmune disease leading to immune activation by pleiotropic effects since they bind to LILRB and KIR family members reducing Treg and MDSC numbers and increased effector T-cell and NK-cell activation, respectively. We have generated an IgG4-HLA-57 open conformer (OC) molecule (iosH2) with high affinity for LILRB molecules and demonstrate its anti-cancer activity in vitro and in vivo.Methods iosH2 was produced by transient gene expression in CHO cells and purified by standard chromatography. Affinity of iosH2 binding was quantified by ELISA and SPR analysis. HLA-G mediated signaling and competition was assessed using functional cell lines. Effect of iosH2 on activation of SHP1/2 was assessed using Western Blot. Functional assays including in vitro polarization and phagocytosis potential of primary macrophages was assessed by flow cytometry in the presence of iosH2 or isotype control. Effect of iosH2 on T cell activation was evaluated in co-cultures of cancer and T cells. Mouse models were used to assess in vivo activity.Results iosH2 binds to LILRB2 with high affinity and blocks the activation of HLA-G. In addition, iosH2 blocks receptor-mediated activation of SHP1/2. iosH2 promotes a shift from M2 to M1 macrophages with enhanced tumor cell phagocytosis in vitro. iosH2 enhances activation and killing potential of T cells in cancer cells and T cells co-culture assay. iosH2 exerts therapeutic efficacy in mouse transgenic (melanoma) and different syngeneic tumor models (e.g. pancreatic, colon and breast cancer) as monotherapy. Moreover, it acts synergistically in vivo with PD1 blocking antibodies achieving long-term tumor control. Ex vivo tumor sample analysis demonstrates a significant reduction of MDSC and Tregs and a shift towards an activated inflammatory M1 macrophage phenotype. Loss of MDSC functionality was paralleled by enhanced CD8+ T cell expansion and activity.Conclusions iosH2 binds to LILRB2 with high affinity, restores immune cell function in vitro and demonstrates anti-tumor activity in different in vivo mouse models. In addition, it acts synergistically in vivo with PD1. iosH2 is a first-in-class OC therapeutic with robust anti-tumor activity by promoting key components of the innate immune system. Clinical development is under way and phase I trial in preparation.

scholarly journals Immune modulation by MANF promotes tissue repair and regenerative success in the retina

Science ◽  
2016 ◽  
Vol 353 (6294) ◽  
pp. aaf3646 ◽  
Author(s):  
Joana Neves ◽  
Jie Zhu ◽  
Pedro Sousa-Victor ◽  
Mia Konjikusic ◽  
Rebeccah Riley ◽  
...  
Keyword(s):  
Immune Cells ◽  
Tissue Repair ◽  
Immune Modulation ◽  
Innate Immune ◽  
Alternative Activation ◽  
Innate Immune Cells ◽  
Tissue Repair And Regeneration ◽  
Promising Strategy ◽  
Repair Mechanisms ◽  
Regenerative Therapies

Regenerative therapies are limited by unfavorable environments in aging and diseased tissues. A promising strategy to improve success is to balance inflammatory and anti-inflammatory signals and enhance endogenous tissue repair mechanisms. Here, we identified a conserved immune modulatory mechanism that governs the interaction between damaged retinal cells and immune cells to promote tissue repair. In damaged retina of flies and mice, platelet-derived growth factor (PDGF)–like signaling induced mesencephalic astrocyte-derived neurotrophic factor (MANF) in innate immune cells. MANF promoted alternative activation of innate immune cells, enhanced neuroprotection and tissue repair, and improved the success of photoreceptor replacement therapies. Thus, immune modulation is required during tissue repair and regeneration. This approach may improve the efficacy of stem-cell–based regenerative therapies.

scholarly journals Natural killer cell activation after infection with lactate dehydrogenase-elevating virus

2002 ◽  
Vol 83 (11) ◽  
pp. 2709-2716 ◽  
Author(s):  
Dominique Markine-Goriaynoff ◽  
Xavier Hulhoven ◽  
César L. Cambiaso ◽  
Philippe Monteyne ◽  
Thérèse Briet ◽  
...  
Keyword(s):  
Immune System ◽  
Lactate Dehydrogenase ◽  
Nk Cells ◽  
Natural Killer ◽  
Innate Immune System ◽  
Cell Activation ◽  
Nk Cell ◽  
Killer Cell ◽  
Innate Immune ◽  
Ifn Γ

Early after infection, lactate dehydrogenase-elevating virus (LDV) alters the immune system by polyclonally activating B lymphocytes, which leads to IgG2a-restricted hypergammaglobulinaemia, and by suppressing the secretion of Th2 cytokines. Considering that these alterations may involve cells of the innate immune system and cytokines such as interferon-gamma (IFN-γ), we analysed the effect of LDV on natural killer (NK) cells. Within a few days of infection, a strong and transient NK cell activation, characterized by enhanced IFN-γ message expression and cytolysis, was observed. LDV triggered a large increase in serum IFN-γ levels. Because NK cells and IFN-γ may participate in the defence against virus infection, we analysed their possible role in the control of LDV titres with a new agglutination assay. Our results indicate that neither the activation of NK cells nor the IFN-γ secretion affect the early and rapid virus replication that follows LDV inoculation.

scholarly journals Is Still's Disease an Autoinflammatory Syndrome?

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Linda Rossi-Semerano ◽  
Isabelle Koné-Paut
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Innate Immune System ◽  
Autoinflammatory Disease ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Innate Immune ◽  
Autoinflammatory Syndrome ◽  
Still’S Disease ◽  
Still's Disease ◽  
Targeted Treatments ◽  
Laboratory Features

Systemic juvenile idiopathic arthritis (sJIA), formerly called Still's disease, is officially classified as a subset of juvenile idiopathic arthritis (JIA). Beside arthritis, it is characterized by prominent systemic features and a marked inflammatory response. Even if it is still included in the group of juvenile arthritides, sJIA is set apart from all the other forms of JIA. This disorder has markedly distinct clinical and laboratory features suggesting a different pathogenesis. sJIA does not show any association with HLA genes or with autoantibodies and is characterised by an uncontrolled activation of phagocytes with hypersecretion of IL-1 and IL-6. Based on clinical and laboratory features, as well as on new acquisitions on the pathogenesis, it seems evident that sJIA is an autoinflammatory disease related to abnormality in innate immune system. The new insights on the pathogenesis of sJIA have therefore dramatically changed the approach to treatment, with the development of targeted treatments (anti-IL-1 and anti-IL-6 agents) more effective and safer than earlier medications.

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