scholarly journals Shaping of Monocyte-Derived Dendritic Cell Development and Function by Environmental Factors in Rheumatoid Arthritis

2021 ◽  
Vol 22 (24) ◽  
pp. 13670
Author(s):  
Frédéric Coutant
Keyword(s):  
Rheumatoid Arthritis ◽  
Environmental Factors ◽  
Osteoclast Differentiation ◽  
Cell Populations ◽  
Molecular Signaling ◽  
Soluble Factors ◽  
Monocyte Differentiation ◽  
Synovial Tissues ◽  
And Function

Dendritic cells (DC) are heterogeneous cell populations essential for both inducing immunity and maintaining immune tolerance. Chronic inflammatory contexts, such as found in rheumatoid arthritis (RA), severely affect the distribution and the function of DC, contributing to defective tolerance and fueling inflammation. In RA, the synovial fluid of patients is enriched by a subset of DC that derive from monocytes (Mo-DC), which promote deleterious Th17 responses. The characterization of environmental factors in the joint that impact on the development and the fate of human Mo-DC is therefore of great importance in RA. When monocytes leave the blood and infiltrate inflamed synovial tissues, the process of differentiation into Mo-DC can be influenced by interactions with soluble factors such as cytokines, local acidosis and dysregulated synoviocytes. Other molecular factors, such as the citrullination process, can also enhance osteoclast differentiation from Mo-DC, favoring bone damages in RA. Conversely, biotherapies used to control inflammation in RA, modulate also the process of monocyte differentiation into DC. The identification of the environmental mediators that control the differentiation of Mo-DC, as well as the underlying molecular signaling pathways, could constitute a major breakthrough for the development of new therapies in RA.

Analysis of cell populations in rheumatoid arthritis synovial tissues

1992 ◽  
Vol 21 (6) ◽  
pp. 393-399 ◽  
Author(s):  
Ghada Yanni ◽  
Alex Whelan ◽  
Conleth Feighery ◽  
Barry Bresnihan
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Populations ◽  
Synovial Tissues

scholarly journals Establishment and characterization of nurse cell-like stromal cell lines from synovial tissues of patients with rheumatoid arthritis

1999 ◽  
Vol 42 (2) ◽  
pp. 221-228 ◽  
Author(s):  
Eiji Takeuchi ◽  
Tetsuya Tomita ◽  
Tomoko Toyosaki-Maeda ◽  
Motoharu Kaneko ◽  
Hiroshi Takano ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Lines ◽  
Stromal Cell ◽  
Nurse Cell ◽  
Synovial Tissues

scholarly journals Interleukin-9 Facilitates Osteoclastogenesis in Rheumatoid Arthritis

2021 ◽  
Vol 22 (19) ◽  
pp. 10397
Author(s):  
Santanu Kar ◽  
Ranjan Gupta ◽  
Rajesh Malhotra ◽  
Vijay Sharma ◽  
Kamran Farooque ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Structural Damage ◽  
Mononuclear Cells ◽  
Osteoclast Differentiation ◽  
Osteoclast Formation ◽  
Expression Of Genes ◽  
Bone Degradation ◽  
Macrophage Colony ◽  
And Function ◽  
Interleukin 9

In rheumatoid arthritis (RA), inflammatory cytokines play a pivotal role in triggering abnormal osteoclastogenesis leading to articular destruction. Recent studies have demonstrated enhanced levels of interleukin-9 (IL-9) in the serum and synovial fluid of patients with RA. In RA, strong correlation has been observed between tissue inflammation and IL-9 expression in synovial tissue. Therefore, we investigated whether IL-9 influences osteoclastogenesis in patients with RA. We conducted the study in active RA patients. For inducing osteoclast differentiation, mononuclear cells were stimulated with soluble receptor activator of NF-kB ligand (sRANKL) and macrophage-colony-stimulating factor (M-CSF) in the presence or absence of recombinant (r) IL-9. IL-9 stimulation significantly enhanced M-CSF/sRANKL-mediated osteoclast formation and function. Transcriptome analysis revealed differential gene expression induced with IL-9 stimulation in the process of osteoclast differentiation. IL-9 mainly modulates the expression of genes, which are involved in the metabolic pathway. Moreover, we observed that IL-9 modulates the expression of matrix metalloproteinases (MMPs), which are critical players in bone degradation. Our results indicate that IL-9 has the potential to influence the structural damage in the RA by promoting osteoclastogenesis and modulating the expression of MMPs. Thus, blocking IL-9 pathways might be an attractive immunotherapeutic target for preventing bone degradation in RA.

scholarly journals CD109 regulates the inflammatory response and is required for the pathogenesis of rheumatoid arthritis

2019 ◽  
Vol 78 (12) ◽  
pp. 1632-1641 ◽  
Author(s):  
Guanhua Song ◽  
Tingting Feng ◽  
Ru Zhao ◽  
Qiqi Lu ◽  
Yutao Diao ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Response ◽  
Osteoclast Differentiation ◽  
Small Interfering Rnas ◽  
Inflammatory Stimuli ◽  
Synovial Tissues ◽  
Factor Α ◽  
Fibroblast Like Synoviocytes

ObjectiveThe aim of this study was to investigate the role of CD109 in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) and to evaluate its potential as a therapeutic target.MethodsCD109 expression was examined in synovial tissues and FLSs from RA patients and collagen-induced arthritis (CIA) model mice. CD109-deficient mice were developed to evaluate the severity of CIA. Small interfering RNAs and a neutralising antibody against CD109 (anti-CD109) were designed for functional or treatment studies in RA FLSs and CIA.ResultsCD109 was found to be abundantly expressed in the synovial tissues from RA patients and CIA mice. CD109 expression in RA FLSs was upregulated by inflammatory stimuli, such as interleukin-1β and tumour necrosis factor-α. Silencing of CD109 or anti-CD109 treatment reduced proinflammatory factor production, cell migration, invasion, chemoattractive potential and osteoclast differentiation, thereby reducing the deleterious inflammatory response of RA FLSs in vitro. Mice lacking CD109 were protected against arthritis in the CIA model. Anti-CD109 treatment prevented the onset and ameliorated the severity of CIA lesions.ConclusionOur study uncovers an antiarthritic role for CD109 and suggests that CD109 inhibition might serve as a promising novel therapeutic strategy for RA.

Joint Destructive Role of Mast Cells in Rheumatoid Arthritis

2020 ◽  
Author(s):  
Kyoung-Woon Kim ◽  
Bo-Mi Kim ◽  
Ji-Yeon Won ◽  
Hong-Ki Min ◽  
Kyung-Ann Lee ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mast Cells ◽  
Therapeutic Option ◽  
Joint Destruction ◽  
Osteoclast Differentiation ◽  
Multinucleated Cells ◽  
Synovial Tissues ◽  
Concentration Levels ◽  
Gene Expression Levels

Abstract Background: We aimed to define the inflammatory and tissue-destructive roles of mast cells in rheumatoid arthritis (RA). Methods: Serum and synovial fluid (SF) concentration levels of tryptase, chymase, and histamine were quantified using ELISA. After activating mast cells using IL-33, the production of TNF-a, IL-1b, IL-6, IL-17, RANKL, and MMPs was determined using real-time PCR and ELISA. Osteoclastogenesis was assessed in CD14+ monocytes from peripheral blood and SF, which were cultured with IL-33-activated mast cells, by counting TRAP-positive multinucleated cells. Results: The concentration levels of serum tryptase, chymase, and histamine and SF histamine were higher in patients with RA than in controls. FceR1 and c-kit-positive mast cells were higher in RA synovium than in osteoarthritic (OA) synovium. Stimulation of mast cells by IL-33 increased the number of trypatse+chymase- and tryptase+chymase+ mast cells. IL-33 stimulation also increased the gene expression levels of TNF-a, IL-1b, IL-6, IL-17, RANKL, and MMP-9 in mast cells. Furthermore, IL-33 stimulated human CD14+ monocytes to differentiate into TRAP+ multinucleated osteoclasts. When CD14+ monocytes were co-cultured with mast cells, osteoclast differentiation was increased. Additionally, IL-33-activated mast cells stimulated osteoclast differentiation. The inhibition of intercellular contact between mast cells and monocytes using inserts reduced osteoclast differentiation. Conclusions: Mast cells and their mediators such as tryptase, chymase, and histamine were increased in RA synovial tissues and fluid. Mast cells stimulated osteoclast differentiation in monocytes. The inhibition of mast cells could be a new therapeutic option for reducing joint destruction in RA.

Functional characterization of human brown adipose tissue metabolism

2020 ◽  
Vol 477 (7) ◽  
pp. 1261-1286 ◽  
Author(s):  
Marie Anne Richard ◽  
Hannah Pallubinsky ◽  
Denis P. Blondin
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Functional Characterization ◽  
Human Infants ◽  
Positron Emission ◽  
Brown Adipose ◽  
Treatment Of Obesity ◽  
And Function

Brown adipose tissue (BAT) has long been described according to its histological features as a multilocular, lipid-containing tissue, light brown in color, that is also responsive to the cold and found especially in hibernating mammals and human infants. Its presence in both hibernators and human infants, combined with its function as a heat-generating organ, raised many questions about its role in humans. Early characterizations of the tissue in humans focused on its progressive atrophy with age and its apparent importance for cold-exposed workers. However, the use of positron emission tomography (PET) with the glucose tracer [18F]fluorodeoxyglucose ([18F]FDG) made it possible to begin characterizing the possible function of BAT in adult humans, and whether it could play a role in the prevention or treatment of obesity and type 2 diabetes (T2D). This review focuses on the in vivo functional characterization of human BAT, the methodological approaches applied to examine these features and addresses critical gaps that remain in moving the field forward. Specifically, we describe the anatomical and biomolecular features of human BAT, the modalities and applications of non-invasive tools such as PET and magnetic resonance imaging coupled with spectroscopy (MRI/MRS) to study BAT morphology and function in vivo, and finally describe the functional characteristics of human BAT that have only been possible through the development and application of such tools.

Parasite defense mechanisms in bees: behavior, immunity, antimicrobials, and symbionts

2019 ◽  
Vol 4 (1) ◽  
pp. 59-76 ◽  
Author(s):  
Alison E. Fowler ◽  
Rebecca E. Irwin ◽  
Lynn S. Adler
Keyword(s):  
Defense Mechanisms ◽  
Poor Quality ◽  
Future Research ◽  
Immune Priming ◽  
Social Bees ◽  
Bee Health ◽  
Landscape Scales ◽  
And Function ◽  
Solitary Species

Parasites are linked to the decline of some bee populations; thus, understanding defense mechanisms has important implications for bee health. Recent advances have improved our understanding of factors mediating bee health ranging from molecular to landscape scales, but often as disparate literatures. Here, we bring together these fields and summarize our current understanding of bee defense mechanisms including immunity, immunization, and transgenerational immune priming in social and solitary species. Additionally, the characterization of microbial diversity and function in some bee taxa has shed light on the importance of microbes for bee health, but we lack information that links microbial communities to parasite infection in most bee species. Studies are beginning to identify how bee defense mechanisms are affected by stressors such as poor-quality diets and pesticides, but further research on this topic is needed. We discuss how integrating research on host traits, microbial partners, and nutrition, as well as improving our knowledge base on wild and semi-social bees, will help inform future research, conservation efforts, and management.

Relationship of HLA-DRB1 Alleles and Rheumatoid Arthritis in West South of Iran

2017 ◽  
Vol 9 (03) ◽  
Author(s):  
Karim Mowla ◽  
Elham Rajaee M. D. ◽  
Mehrdad Dargahi-MalAmir M. D. ◽  
Neda Yousefinezhad ◽  
Maryam Jamali Hondori
Keyword(s):  
Rheumatoid Arthritis ◽  
Environmental Factors ◽  
Rheumatoid Factor ◽  
Dna Extraction ◽  
Wrist Joint ◽  
Blood Sampling ◽  
Healthy Controls ◽  
Relationship Of ◽  
Synovial Pannus

Background: Rheumatoid arthritis is a systemic multifactor disease that presented with symmetrical polyarthritis more preferably in small wrist joint and ankle. Synovial pannus cause destruction and deformities in joints. The main reason of this disease in unknown, but past researchesshowed that genetically factor play important role beside environmental factors in susceptibility to this entity. Method:100 patients with rheumatoid arthritis diagnosed upon ACR 2010 criteria enrolled study. 92 healthy patents also enrolled DNA studying. of both group was extracted through DNA extraction kits by blood sampling. HLA-DRB1 typing was done by PCR-SSP method. Results: There were no significant differences in HLADRB1 *04, HLADRB1*08 and HLADRB1*11 alleles presentation between patients and healthy controls. Only there were statically significant correlation between HLA-DRB1*08 and Rheumatoid factor positive patents. (P = 0.025).

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