The Adipokine Network in Rheumatic Joint Diseases

Rheumatic diseases encompass a diverse group of chronic disorders that commonly affect musculoskeletal structures. Osteoarthritis (OA) and rheumatoid arthritis (RA) are the two most common, leading to considerable functional limitations and irreversible disability when patients are unsuccessfully treated. Although the specific causes of many rheumatic conditions remain unknown, it is generally accepted that immune mechanisms and/or uncontrolled inflammatory responses are involved in their etiology and symptomatology. In this regard, the bidirectional communication between neuroendocrine and immune system has been demonstrated to provide a homeostatic network that is involved in several pathological conditions. Adipokines represent a wide variety of bioactive, immune and inflammatory mediators mainly released by adipocytes that act as signal molecules in the neuroendocrine-immune interactions. Adipokines can also be synthesized by synoviocytes, osteoclasts, osteoblasts, chondrocytes and inflammatory cells in the joint microenvironment, showing potent modulatory properties on different effector cells in OA and RA pathogenesis. Effects of adiponectin, leptin, resistin and visfatin on local and systemic inflammation are broadly described. However, more recently, other adipokines, such as progranulin, chemerin, lipocalin-2, vaspin, omentin-1 and nesfatin, have been recognized to display immunomodulatory actions in rheumatic diseases. This review highlights the latest relevant findings on the role of the adipokine network in the pathophysiology of OA and RA.

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Airways inflammatory and atopy-related responses in athletes

South African Journal of Sports Medicine ◽

10.17159/2413-3108/2006/v18i2a243 ◽

2009 ◽

Vol 18 (2) ◽

pp. 46 ◽

Cited By ~ 1

Author(s):

AJ McKune ◽

LL Smith

Keyword(s):

South African ◽

Sports Medicine ◽

Inflammatory Responses ◽

Cell Damage ◽

Inflammatory Cells ◽

Endurance Athletes ◽

Airway Trauma ◽

Airway Symptoms ◽

Cytokine Milieu

The prevalence of asthma and airway hyperresponsiveness (AHR) in highly trained endurance athletes is rising. The type of training (i.e. endurance, or speed and power) seems to influence the airway symptoms. High-intensity exercise and training might contribute to the development of asthma or AHR in athletes previously unaffected by these airway disorders. Repeated hyperventilation of unconditioned air, as well as air containing irritants and/or allergens has been suggested to cause thermal, mechanical, or osmotic airway trauma resulting in damage to the airway epithelium. Subsequent airway inflammatory responses may be responsible for the development of atopy-related symptoms in endurance athletes such as those observed in asthma and AHR. Eosinophils and neutrophils are the inflammatory cells that have been frequently observed to be elevated in the airways of endurance athletes. The trafficking of these cells to the airways may possibly be regulated by TH2 cytokines that are expressed in the airways in response to epithelial cell damage. In addition, these airway inflammatory responses may lead to airway remodelling similar to that which occurs in asthma. The effect of the exercise challenge itself may initiate airway atopy-related and inflammatory responses in endurance athletes. While the literature seems to support the role of local airway conditions and/or events in inducing atopy-related symptoms in athletes, it is proposed that alterations in the hormonal and/or cytokine milieu with intense competition and/or training may also play a role. South African Journal of Sports Medicine Vol. 18 (2) 2006: pp. 46-51

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Targeting Mononuclear Phagocyte Receptors in Cancer Immunotherapy: New Perspectives of the Triggering Receptor Expressed on Myeloid Cells (TREM-1)

Cancers ◽

10.3390/cancers12051337 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1337

Author(s):

Federica Raggi ◽

Maria Bosco

Keyword(s):

Tumor Progression ◽

Cancer Immunotherapy ◽

Inflammatory Responses ◽

Inflammatory Cells ◽

Therapeutic Strategies ◽

Mononuclear Phagocyte ◽

Mononuclear Phagocytes ◽

Receptor Expression ◽

Tumor Phenotype

Inflammatory cells are major players in the onset of cancer. The degree of inflammation and type of inflammatory cells in the tumor microenvironment (TME) are responsible for tilting the balance between tumor progression and regression. Cancer-related inflammation has also been shown to influence the efficacy of conventional therapy. Mononuclear phagocytes (MPs) represent a major component of the inflammatory circuit that promotes tumor progression. Despite their potential to activate immunosurveillance and exert anti-tumor responses, MPs are subverted by the tumor to support its growth, immune evasion, and spread. MP responses in the TME are dictated by a network of stimuli integrated through the cross-talk between activatory and inhibitory receptors. Alterations in receptor expression/signaling can create excessive inflammation and, when chronic, promote tumorigenesis. Research advances have led to the development of new therapeutic strategies aimed at receptor targeting to induce a tumor-infiltrating MP switch from a cancer-supportive toward an anti-tumor phenotype, demonstrating efficacy in different human cancers. This review provides an overview of the role of MP receptors in inflammation-mediated carcinogenesis and discusses the most recent updates regarding their targeting for immunotherapeutic purposes. We focus in particular on the TREM-1 receptor, a major amplifier of MP inflammatory responses, highlighting its relevance in the development and progression of several types of inflammation-associated malignancies and the promises of its inhibition for cancer immunotherapy.

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Platelets as Modulators of Inflammation

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0037-1607432 ◽

2017 ◽

Vol 44 (02) ◽

pp. 091-101 ◽

Cited By ~ 16

Author(s):

Seok-Joo Kim ◽

Rachelle Davis ◽

Craig Jenne

Keyword(s):

Endothelial Cell ◽

Tissue Damage ◽

Inflammatory Responses ◽

Platelet Response ◽

Platelet Activity ◽

Disease Pathogenesis ◽

Innate And Adaptive Immunity ◽

Effector Cells ◽

Cell Responses

AbstractPlatelets have classically been considered crucial effector cells in hemostasis, but now are increasingly recognized as players during inflammatory responses in innate and adaptive immunity. Platelets can recognize and kill invading pathogens, and, upon stimulation, also release a wide array of mediators that modify immune and endothelial cell responses. Increased platelet activity can protect the host against infectious insults; however, the excessive activity can lead to inflammation-mediated tissue damage. These critical roles highlight the necessity of balancing the platelet response at the intersection of hemostasis and inflammation. In this review, the authors present the current understanding of the inflammatory role of platelets. They also highlight recent findings on a modulator that links inflammation and deleterious tissue damage in disease pathogenesis.

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Airways inflammatory and atopy-related responses in athletes

South African Journal of Sports Medicine ◽

10.17159/2078-516x/2006/v18i2a243 ◽

2006 ◽

Vol 18 (2) ◽

pp. 46

Author(s):

AJ McKune ◽

LL Smith

Keyword(s):

South African ◽

Sports Medicine ◽

Inflammatory Responses ◽

Cell Damage ◽

Inflammatory Cells ◽

Endurance Athletes ◽

Airway Trauma ◽

Airway Symptoms ◽

Cytokine Milieu

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IL-33 in Rheumatic Diseases

Frontiers in Medicine ◽

10.3389/fmed.2021.739489 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yuanji Dong ◽

Jixin Zhong ◽

Lingli Dong

Keyword(s):

Rheumatic Diseases ◽

Lupus Erythematosus ◽

Nk Cell ◽

Killer Cell ◽

Inflammatory Cells ◽

Protective Role ◽

Cell Group ◽

Cancer Tissue ◽

Interleukin 33

Interleukin-33 (IL-33) is a nuclear factor mainly expressed in barrier epithelium, endothelial cells, and fibroblast reticular cells. Some inflammatory cells also express IL-33 under certain conditions. The important role of IL-33 in allergic reactions, helminth infection, cancer, tissue fibrosis, chronic inflammation, organ transplantation, and rheumatic immune diseases has been extensively studied in recent years. IL-33 primarily activates various circulating and tissue-resident immune cells, including mast cell, group 2 innate lymphoid cell (ILC2), regulatory T cell (Treg), T helper 2 cell (Th2), natural killer cell (NK cell), and macrophage. Therefore, IL-33 plays an immunomodulatory role and shows pleiotropic activity in different immune microenvironments. The IL-33/serum stimulation-2 (ST2) axis has been shown to have a detrimental effect on rheumatoid arthritis, systemic lupus erythematosus, and other rheumatic diseases. Interestingly, IL-33 also plays a protective role in the repair of barrier epithelium and the activation of Tregs. Therefore, the role of IL-33/ST2 depends on the underlying pathological conditions in rheumatic diseases. This review focuses on the dual role of the IL-33/ST2 axis in rheumatic diseases.

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Responses of Mast Cells to Pathogens: Beneficial and Detrimental Roles

Frontiers in Immunology ◽

10.3389/fimmu.2021.685865 ◽

2021 ◽

Vol 12 ◽

Author(s):

Mariela Jiménez ◽

Daniel Cervantes-García ◽

Laura E. Córdova-Dávalos ◽

Marian Jesabel Pérez-Rodríguez ◽

Claudia Gonzalez-Espinosa ◽

...

Keyword(s):

Mast Cells ◽

Current Knowledge ◽

Inflammatory Cells ◽

Biologically Active ◽

Matrix Remodeling ◽

Effector Cells ◽

Antimicrobial Substances ◽

Microbial Destruction ◽

Pathogen Clearance

Mast cells (MCs) are strategically located in tissues close to the external environment, being one of the first immune cells to interact with invading pathogens. They are long living effector cells equipped with different receptors that allow microbial recognition. Once activated, MCs release numerous biologically active mediators in the site of pathogen contact, which induce vascular endothelium modification, inflammation development and extracellular matrix remodeling. Efficient and direct antimicrobial mechanisms of MCs involve phagocytosis with oxidative and non-oxidative microbial destruction, extracellular trap formation, and the release of antimicrobial substances. MCs also contribute to host defense through the attraction and activation of phagocytic and inflammatory cells, shaping the innate and adaptive immune responses. However, as part of their response to pathogens and under an impaired, sustained, or systemic activation, MCs may contribute to tissue damage. This review will focus on the current knowledge about direct and indirect contribution of MCs to pathogen clearance. Antimicrobial mechanisms of MCs are addressed with special attention to signaling pathways involved and molecular weapons implicated. The role of MCs in a dysregulated host response that can increase morbidity and mortality is also reviewed and discussed, highlighting the complexity of MCs biology in the context of host-pathogen interactions.

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Perforin-Deficient CD8+ T Cells Mediate Fatal Lymphocytic Choriomeningitis despite Impaired Cytokine Production

Journal of Virology ◽

10.1128/jvi.80.3.1222-1230.2006 ◽

2006 ◽

Vol 80 (3) ◽

pp. 1222-1230 ◽

Cited By ~ 15

Author(s):

Pernille Storm ◽

Christina Bartholdy ◽

Maria Rathman Sørensen ◽

Jan Pravsgaard Christensen ◽

Allan Randrup Thomsen

Keyword(s):

T Cells ◽

Inflammatory Cells ◽

Lymphocytic Choriomeningitis ◽

Effector T Cells ◽

Fatal Disease ◽

Effector Cells ◽

Proinflammatory Mediators ◽

The Central Nervous System ◽

Deficient Mice

ABSTRACT Intracerebral (i.c.) infection with lymphocytic choriomeningitis virus (LCMV) is one of the most studied models for virus-induced immunopathology, and based on results from perforin-deficient mice, it is currently assumed that fatal disease directly reflects perforin-mediated cell lysis. However, recent studies have revealed additional functional defects within the effector T cells of LCMV-infected perforin-deficient mice, raising the possibility that perforin may not be directly involved in mediating lethal disease. For this reason, we decided to reevaluate the role of perforin in determining the outcome of i.c. infection with LCMV. We confirmed that the expansion of virus-specific CD8+ T cells is unimpaired in perforin-deficient mice. However, despite the fact that the virus-specific CD8+ effector T cells in perforin-deficient mice are broadly impaired in their effector function, these mice invariably succumb to i.c. infection with LCMV strain Armstrong, although a few days later than matched wild-type mice. Upon further investigation, we found that this delay correlates with the delayed recruitment of inflammatory cells to the central nervous system (CNS). However, CD8+ effector T cells were not kept from the CNS by sequestering in infected extraneural organ sites such as liver or lungs. Thus, the observed dysfunctionality regarding the production of proinflammatory mediators probably results in the delayed recruitment of effector cells to the CNS, and this appears to be the main explanation for the delayed onset of fatal disease in perforin-deficient mice. However, once accumulated in the CNS, virus-specific CD8+ T cells can induce fatal CNS pathology despite the absence of perforin-mediated lysis and reduced capacity to produce several key cytokines.

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Role of placental inflammatory mediators and growth factors in patients with rheumatic diseases with a focus on systemic sclerosis

Rheumatology ◽

10.1093/rheumatology/keaa782 ◽

2020 ◽

Author(s):

Francesca Motta ◽

Veronica Codullo ◽

Véronique Ramoni ◽

Stefania Cesari ◽

Giuseppina Ferrario ◽

...

Keyword(s):

Growth Factors ◽

Rheumatic Diseases ◽

Inflammatory Mediators ◽

Inflammatory Cells ◽

Obstetric Complications ◽

Histopathological Analysis ◽

Increased Risk ◽

Leucocyte Infiltration ◽

Hepatocyte Growth

Abstract Objectives Pregnancy in SSc is burdened with an increased risk of obstetric complications. Little is known about the underlying placental alterations. This study aimed to better understand pathological changes and the role of inflammation in SSc placentas. Leucocyte infiltration, inflammatory mediators and atypical chemokine receptor 2 (ACKR2) expression in SSc placentas were compared with those in other rheumatic diseases (ORD) and healthy controls (HC). Methods A case–control study was conducted on eight pregnant SSc patients compared with 16 patients with ORD and 16 HC matched for gestational age. Clinical data were collected. Placentas were obtained for histopathological analysis and immunohistochemistry (CD3, CD20, CD11c, CD68, ACKR2). Samples from four SSc, eight ORD and eight HC were analysed by qPCR for ACKR2 expression and by multiplex assay for cytokines, chemokines and growth factors involved in angiogenesis and inflammation. Results The number of placental CD3, CD68 and CD11 cells was significantly higher in patients affected by rheumatic diseases (SSc+ORD) compared with HC. Hepatocyte growth factor was significantly increased in the group of rheumatic diseases patients (SSc+ORD) compared with HC, while chemokine (C-C motif) ligand 5 (CCL5) was significantly higher in SSc patients compared with ORD and HC. CCL5 levels directly correlated with the number of all local inflammatory cells and higher levels were associated with histological villitis. Conclusions Inflammatory alterations characterize placentas from rheumatic disease patients and could predispose to obstetric complications in these subjects.

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Perivascular Inflammation in Pulmonary Arterial Hypertension

Cells ◽

10.3390/cells9112338 ◽

2020 ◽

Vol 9 (11) ◽

pp. 2338

Author(s):

Yijie Hu ◽

Leon Chi ◽

Wolfgang M Kuebler ◽

Neil M Goldenberg

Keyword(s):

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Inflammatory Mediators ◽

Inflammatory Responses ◽

Inflammatory Cells ◽

Cytokines And Chemokines ◽

Perivascular Inflammation ◽

Pulmonary Arterial ◽

Parenchymal Cells

Perivascular inflammation is a prominent pathologic feature in most animal models of pulmonary hypertension (PH) as well as in pulmonary arterial hypertension (PAH) patients. Accumulating evidence suggests a functional role of perivascular inflammation in the initiation and/or progression of PAH and pulmonary vascular remodeling. High levels of cytokines, chemokines, and inflammatory mediators can be detected in PAH patients and correlate with clinical outcome. Similarly, multiple immune cells, including neutrophils, macrophages, dendritic cells, mast cells, T lymphocytes, and B lymphocytes characteristically accumulate around pulmonary vessels in PAH. Concomitantly, vascular and parenchymal cells including endothelial cells, smooth muscle cells, and fibroblasts change their phenotype, resulting in altered sensitivity to inflammatory triggers and their enhanced capacity to stage inflammatory responses themselves, as well as the active secretion of cytokines and chemokines. The growing recognition of the interaction between inflammatory cells, vascular cells, and inflammatory mediators may provide important clues for the development of novel, safe, and effective immunotargeted therapies in PAH.

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Human IL-23R Cytokine-Binding Homology Region-Fc Fusion Protein Ameliorates Psoriasis via the Decrease of Systemic Th17 and ILC3 Cell Responses

International Journal of Molecular Sciences ◽

10.3390/ijms20174170 ◽

2019 ◽

Vol 20 (17) ◽

pp. 4170 ◽

Cited By ~ 1

Author(s):

Yue Gao ◽

Zhengying Bian ◽

Wenyao Xue ◽

Qianwen Li ◽

Yu Zeng ◽

...

Keyword(s):

Fusion Protein ◽

Inflammatory Responses ◽

Inflammatory Cells ◽

Inflammatory Factors ◽

Cell Responses ◽

Adaptive Immune ◽

Immune Mediated ◽

Fc Fusion Protein ◽

Shed Light

Interleukin (IL)-23 is considered an effective therapeutic target for the treatment of psoriasis because of the crucial role of the IL-23/IL-17 axis in the pathogenesis of psoriasis, and it has recently been reported to be involved in ILC3 cell differentiation. In this study, we report that eukaryotically expressed rhIL23R-CHR/Fc, as an endogenous extracellular receptor analogue, could be a natural antagonist in an imiquimod (IMQ)-induced psoriasis-like mouse model, including the antagonizing effect of suppressed inflammation in the skin lesion, decreased production of pro-inflammatory cells, and reduced the expression of pro-inflammatory factors. The rhIL23R-CHR/Fc fusion protein inhibits both innate immune and adaptive immune-mediated inflammatory responses. These findings shed light on rhIL23R-CHR/Fc as a promising candidate therapy for the treatment of psoriasis.

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