Pathogenesis of polymyalgia rheumatica

Polymyalgia rheumatica (PMR) is a chronic, inflammatory disorder of unknown cause, almost exclusively occurring in people aged over 50 and often associated with giant cell arteritis. The evidence that PMR occurs almost exclusively in individuals aged over 50 may indicate that age-related immune alterations in genetically predisposed subjects contribute to development of the disease. Several infectious agents have been investigated as possible triggers of PMR even though the results are inconclusive. Activation of the innate and adaptive immune systems has been proved in PMR patients as demonstrated by the activation of dendritic cells and monocytes/macrophages and the altered balance between Th17 and Treg cells. Disturbed B cell distribution and function have been also demonstrated in PMR patients suggesting a pathogenesis more complex than previously imagined. In this review we will discuss the recent findings regarding the pathogenesis of PMR.

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Imaging in polymyalgia rheumatica

Reumatismo ◽

10.4081/reumatismo.2018.1040 ◽

2018 ◽

Vol 70 (1) ◽

pp. 51 ◽

Cited By ~ 3

Author(s):

N. Possemato ◽

C. Salvarani ◽

N. Pipitone

Keyword(s):

Polymyalgia Rheumatica ◽

Morning Stiffness ◽

Imaging Techniques ◽

Review Article ◽

Inflammatory Disorder ◽

Chronic Inflammatory Disorder ◽

Pet Ct ◽

Ct And Mri

Polymyalgia rheumatica (PMR) is a chronic, inflammatory disorder of unknown cause clinically characterized by pain and prolonged morning stiffness affecting the shoulders and often the pelvic girdle and neck. Imaging has substantially contributed to defining PMR as a disease mainly involving extra-articular structures. This review article analyses the role of the different imaging techniques in the diagnosis and follow-up of patients with PMR with particular emphasis on the role of ultrasound, PET/CT and MRI.

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Optimization of Methods for the Accurate Characterization of Whole Blood Neutrophils

10.21203/rs.3.rs-959537/v1 ◽

2021 ◽

Author(s):

Ashley N. Connelly ◽

Richard P.H. Huijbregts ◽

Harish C. Pal ◽

Valeriya Kuznetsova ◽

Marcus D. Davis ◽

...

Keyword(s):

Whole Blood ◽

Neutrophil Activation ◽

Immune Defense ◽

Experimental Conditions ◽

Adaptive Immune ◽

Blood Neutrophils ◽

One Step ◽

And Function ◽

Adaptive Immune Systems

Abstract Neutrophils are the most abundant circulating leukocyte population with critical roles in immune defense, regulation of innate and adaptive immune systems, and disease pathogenesis. Our progress in understanding precise mechanisms of neutrophil activation, recruitment, and function has been hampered by the lack of optimized and standardized methods for the characterization and phenotyping of this readily activated population. By comparing eight methods of neutrophil characterization, we demonstrate that the level of neutrophil activation and degranulation is associated with specific experimental conditions and the number and type of manipulation steps employed. Staining whole blood at 4ºC and removal of remaining unbound antibodies prior to one-step fixation and red blood cell lysis minimizes neutrophil activation, decreases phenotypic alterations during processing, and prevents nonspecific antibody binding. The effects of anticoagulants used for collection, processing delays, and time and temperature during sample analysis on neutrophil phenotype are addressed. The presented data provide a foundation for higher quality standards of neutrophil characterization improving consistency and reproducibility among studies.

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Natural killer T cells in lipoprotein metabolism and atherosclerosis

Thrombosis and Haemostasis ◽

10.1160/th11-05-0336 ◽

2011 ◽

Vol 106 (11) ◽

pp. 814-819 ◽

Cited By ~ 28

Author(s):

Godfrey Getz ◽

Paul VanderLaan ◽

Catherine Reardon

Keyword(s):

T Cells ◽

T Cell ◽

Natural Killer ◽

Cell Receptor ◽

Nkt Cells ◽

Inflammatory Disorder ◽

Chronic Inflammatory Disorder ◽

Invariant Nkt Cells ◽

Adaptive Immune ◽

Natural Killer T

SummaryCells of both the innate and adaptive immune system participate in the development of atherosclerosis, a chronic inflammatory disorder of medium and large arteries. Natural killer T (NKT) cells express surface markers characteristic of natural killer cells and conventional T cells and bridge the innate and adaptive immune systems. The development and activation of NKT cells is dependent upon CD1d, a MHC-class I-type molecule that presents lipids, especially glycolipids to the T cell receptors on NKT cells. There are two classes of NKT cells; invariant NKT cells that express a semi-invariant T cell receptor and variant NKT cells. This review summarises studies in murine models in which the effect of the activation, overexpression or deletion of NKT cells or only invariant NKT cells on atherosclerosis has been examined.

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Interleukin-23 drives innate and T cell–mediated intestinal inflammation

Journal of Experimental Medicine ◽

10.1084/jem.20061099 ◽

2006 ◽

Vol 203 (11) ◽

pp. 2473-2483 ◽

Cited By ~ 592

Author(s):

Sophie Hue ◽

Philip Ahern ◽

Sofia Buonocore ◽

Marika C. Kullberg ◽

Daniel J. Cua ◽

...

Keyword(s):

T Cell ◽

Intestinal Inflammation ◽

Inflammatory Responses ◽

Inflammatory Disorder ◽

Chronic Inflammatory Disorder ◽

Adaptive Immune ◽

Proinflammatory Responses ◽

Interleukin 23 ◽

Immune Pathology ◽

Chronic Intestinal Inflammation

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract involving aberrant activation of innate and adaptive immune responses. We have used two complementary models of IBD to examine the roles of interleukin (IL)-12 family cytokines in bacterially induced intestinal inflammation. Our results clearly show that IL-23, but not IL-12, is essential for the induction of chronic intestinal inflammation mediated by innate or adaptive immune mechanisms. Depletion of IL-23 was associated with decreased proinflammatory responses in the intestine but had little impact on systemic T cell inflammatory responses. These results newly identify IL-23 as a driver of innate immune pathology in the intestine and suggest that selective targeting of IL-23 represents an attractive therapeutic approach in human IBD.

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Adaptive Immune Responses in Primary Cutaneous Sarcoidosis

Clinical and Developmental Immunology ◽

10.1155/2011/235142 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6 ◽

Cited By ~ 7

Author(s):

Matteo Bordignon ◽

Paola Rottoli ◽

Carlo Agostini ◽

Mauro Alaibac

Keyword(s):

Dendritic Cells ◽

Treatment Strategies ◽

Immunological Response ◽

Inflammatory Disorder ◽

Cutaneous Sarcoidosis ◽

Cutaneous Lesions ◽

Adaptive Immune ◽

Immunological Mechanisms ◽

Adaptive Immune Systems

Sarcoidosis is a multisystemic inflammatory disorder with cutaneous lesions present in about one-quarter of the patients. Cutaneous lesions have been classified as specific and nonspecific, depending on the presence of nonnecrotizing epithelial cell granulomas on histologic studies. The development and progression of specific cutaneous sarcoidosis involves a complex interaction between cells of the adaptive immune systems, notably T-lymphocytes and dendritic cells. In this paper, we will discuss the role of T-cells and skin dendritic cells in the development of primary cutaneous sarcoidosis and comment on the potential antigenic stimuli that may account for the development of the immunological response. We will further explore the contributions of selected cytokines to the immunopathological process. The knowledge of the adaptive immunological mechanisms operative in cutaneous sarcoidosis may subsequently be useful for identifying prevention and treatment strategies of systemic sarcoidosis.

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Macrophages inhibit and enhance endometriosis depending on their origin

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2013776118 ◽

2021 ◽

Vol 118 (6) ◽

pp. e2013776118 ◽

Cited By ~ 1

Author(s):

Chloe Hogg ◽

Kavita Panir ◽

Priya Dhami ◽

Matthew Rosser ◽

Matthias Mack ◽

...

Keyword(s):

Mouse Model ◽

Disease Progression ◽

Peritoneal Macrophage ◽

Peritoneal Macrophages ◽

Inflammatory Disorder ◽

Chronic Inflammatory Disorder ◽

Macrophage Depletion ◽

Monocyte Recruitment ◽

Macrophage Populations ◽

And Function

Macrophages are intimately involved in the pathophysiology of endometriosis, a chronic inflammatory disorder characterized by the growth of endometrial-like tissue (lesions) outside the uterus. By combining genetic and pharmacological monocyte and macrophage depletion strategies we determined the ontogeny and function of macrophages in a mouse model of induced endometriosis. We demonstrate that lesion-resident macrophages are derived from eutopic endometrial tissue, infiltrating large peritoneal macrophages (LpM) and monocytes. Furthermore, we found endometriosis to trigger continuous recruitment of monocytes and expansion of CCR2+ LpM. Depletion of eutopic endometrial macrophages results in smaller endometriosis lesions, whereas constitutive inhibition of monocyte recruitment significantly reduces peritoneal macrophage populations and increases the number of lesions. Reprogramming the ontogeny of peritoneal macrophages such that embryo-derived LpM are replaced by monocyte-derived LpM decreases the number of lesions that develop. We propose a putative model whereby endometrial macrophages are “proendometriosis” while newly recruited monocyte-derived macrophages, possibly in LpM form, are “antiendometriosis.” These observations highlight the importance of monocyte-derived macrophages in limiting disease progression.

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FC-98 Regulates TLR9-Mediated of CXCL-10 Expression in Dendritic Cells via MAPK and STAT1 Signaling Pathway

BioMed Research International ◽

10.1155/2014/926130 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Yonghong Yang ◽

Huan Dou ◽

Xiaoqin Li ◽

Yuxian Song ◽

Wei Gong ◽

...

Keyword(s):

Dendritic Cells ◽

Surface Markers ◽

Toll Like Receptor ◽

Cpg Dna ◽

Bacterial Dna ◽

Adaptive Immune ◽

Stat1 Signaling ◽

And Function ◽

Antigen Presenting ◽

Adaptive Immune Systems

Dendritic cells (DCs), as the most potent professional antigen presenting cells, play a crucial role in both innate and adaptive immune systems. Genomic bacterial DNA mimicked by unmethylated CpG motifs is discovered to possess immunostimulatory effects. CpG-DNA recognized by Toll-like receptor 9 (TLR9) on DCs arouses many immune diseases (such as cancer, viral infection, and autoimmune disorders). In this study we investigated the effects of FC-98 on CpG-induced bone marrow-derived DCs (BMDCs). The results showed that FC-98 significantly inhibited the CpG-induced BMDCs maturation and function by suppressing the expression of surface markers (CD40, CD80, CD86, and MHCII). Moreover, FC-98 downregulated the expression of C-X-C motif chemokine 10 (CXCL-10) both at the mRNA and protein level after CpG induction. Meanwhile, FC-98 markedly affected the migration of BMDCs to T cells without affecting their endocytosis capacity. Furthermore, FC-98 was confirmed to decrease CXCL-10 expression by inhibiting CpG-induced activation of MAPKs (ERK, JNK, and p38) and STAT1 signaling. Overall, these results suggested that FC-98 was a potential molecule in the treatment of CXCL-10-mediated immune diseases.

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Microencapsulated Recombinant Human Epidermal Growth Factor Ameliorates Osteoarthritis in a Murine Model

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/9163279 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Shih-Chao Lin ◽

Xiang Zhang ◽

Shiow-Yi Chen ◽

Chi-Chien Lin ◽

Yen-Shuo Chiu

Keyword(s):

Growth Factor ◽

Epidermal Growth Factor ◽

Platelet Rich Plasma ◽

Therapeutic Effects ◽

Inflammatory Disorder ◽

Chronic Inflammatory Disorder ◽

Human Epidermal Growth Factor ◽

Age Related ◽

Epidermal Growth

Osteoarthritis, a highly age-related and chronic inflammatory disorder with cartilage loss, causes patients difficultly in movement; there is no efficient and sustainable remedy for osteoarthritis currently. Although hyaluronic acid (HA) and platelet-rich plasma (PRP) have been used to alleviate osteoarthritis, the effects could be short and multiple injections might be required. To address this issue, we exploited the property of chitosan to encapsulate recombinant human epidermal growth factor and obtained microencapsulated rhEGF (Me-rhEGF). In the current study, we induced the osteoarthritis-like symptoms with monosodium iodoacetate (MIA) in rats and investigated the therapeutic effects of Me-rhEGF. Following administration of HA/Me-rhEGF in vivo, we observed that the total Mankin scores, cartilage oligomeric protein, C-telopeptide of type II collagen, IL-1β, IL-6, IL-17A, and TNF-α cytokines, nitric oxide, and prostaglandin E2 expressions were significantly inhibited. Our results also strongly indicate that individual use of HA or rhEGF slightly decreased the inflammation and restored the destructive joint structure, but was not as drastic as seen in the HA/Me-rhEGF. Moreover, HA/Me-rhEGF profoundly reduced cartilage destruction and proteoglycan loss and downregulated matrix metalloproteinase expressions. These findings reveal that the treatment of HA/Me-rhEGF could be more beneficial than the use of single HA or rhEGF in reliving osteoarthritis and demonstrate the therapeutic application of microencapsulation technology in difficult joint disorders. In essence, we believe that the Me-rhEGF could be promising for further research and development as a clinical treatment against osteoarthritis.

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Antigen-Induced Immunomodulation in the Pathogenesis of Atherosclerosis

Clinical and Developmental Immunology ◽

10.1155/2008/723539 ◽

2008 ◽

Vol 2008 ◽

pp. 1-15 ◽

Cited By ~ 22

Author(s):

Natalia Milioti ◽

Alexandra Bermudez-Fajardo ◽

Manuel L. Penichet ◽

Ernesto Oviedo-Orta

Keyword(s):

Immune Responses ◽

Atherosclerotic Plaque ◽

Chlamydia Pneumoniae ◽

Artery Occlusion ◽

Atherosclerotic Plaques ◽

Inflammatory Disorder ◽

Chronic Inflammatory Disorder ◽

Adaptive Immune ◽

Protein Components ◽

Shock Proteins

Atherosclerosis is a chronic inflammatory disorder characterised by the accumulation of monocytes/macrophages, smooth muscle cells, and lymphocytes within the arterial wall in response to the release of proinflammatory molecules. Such accumulation results in the formation of the atherosclerotic plaque, which would eventually evolve to complications such as total artery occlusion, rupture, calcification, or aneurysm. Although the molecular mechanism responsible for the development of atherosclerosis is not completely understood, it is clear that the immune system plays a key role in the development of the atherosclerotic plaque and in its complications. There are multiple antigenic stimuli that have been associated with the pathogenesis of atherosclerosis. Most of these stimuli come from modified self-molecules such as oxidised low-density lipoproteins (oxLDLs), beta2glycoprotein1 (2GP1), lipoprotein a (LP(a)), heat shock proteins (HSPs), and protein components of the extracellular matrix such as collagen and fibrinogen in the form of advanced glycation-end (AGE) products. In addition, several foreign antigens including bacteria such as Porphyromonas gingivalis and Chlamydia pneumoniae and viruses such as enterovirus and cytomegalovirus have been associated with atherosclerosis as potentially causative or bystander participants, adding another level of complexity to the analysis of the pathophysiology of atherosclerosis. The present review summarises the most important scientific findings published within the last two decades on the importance of antigens, antigen stimulation, and adaptive immune responses in the development of atherosclerotic plaques.

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Macrophages inhibit and enhance endometriosis depending on their origin

10.1101/2020.04.30.070003 ◽

2020 ◽

Author(s):

Chloe Hogg ◽

Priya Dhami ◽

Matthew Rosser ◽

Matthias Mack ◽

Daniel Soong ◽

...

Keyword(s):

Mouse Model ◽

Disease Progression ◽

Peritoneal Macrophage ◽

Peritoneal Macrophages ◽

Inflammatory Disorder ◽

Chronic Inflammatory Disorder ◽

Macrophage Depletion ◽

Monocyte Recruitment ◽

Macrophage Populations ◽

And Function

AbstractMacrophages are intimately involved in the pathophysiology of endometriosis, a chronic inflammatory disorder characterized by the growth of endometrial-like tissue (lesions) outside the uterus. By combining genetic and pharmacological monocyte and macrophage depletion strategies we determined the ontogeny and function of macrophages in a mouse model of induced endometriosis. We demonstrate that lesion-resident macrophages are derived from eutopic endometrial tissue, infiltrating large peritoneal macrophages (LpM) and monocytes. Furthermore, we found endometriosis to trigger continuous recruitment of monocytes and expansion of CCR2+ LpM. Depletion of eutopic endometrial macrophages results in smaller endometriosis lesions, whereas constitutive inhibition of monocyte recruitment significantly reduces peritoneal macrophage populations and increased the number of lesions. We propose a putative model whereby endometrial macrophages are pro-endometriosis whilst newly-recruited monocyte-derived macrophages, possibly in LpM form, are ‘anti-endometriosis’. These observations highlight the importance of monocyte-derived macrophages in limiting disease progression.

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