Novel Insights into the Ontogenetic and Functional Heterogeneity of Macrophages in Synovial Tissue and Bone

2021 ◽  
Vol 30 (04) ◽  
pp. 292-298
Author(s):  
Gulce Itir Percin ◽  
Anika Grüneboom ◽  
Claudia Waskow ◽  
Stephan Culemann
Keyword(s):  
Immune System ◽  
Synovial Tissue ◽  
Single Cell Analysis ◽  
Bone Erosion ◽  
Imaging Techniques ◽  
Cartilage Destruction ◽  
Innate Immune ◽  
Cell Analysis ◽  
Functional Heterogeneity ◽  
Advanced Imaging

AbstractInflammatory joint diseases like rheumatoid arthritis (RA) belong to the most prevalent autoimmune disorders. RA is characterized by a massive infiltration of immune cells into synovial tissue, cartilage destruction and bone erosion. The perpetuating inflammatory and destructive milieu is associated with severe pain and culminates in complete disability of synovial joints. The events initiating RA are still not fully understood and the treatments are mainly confined to strategies that modify and inhibit the body’s immune system. Macrophages and osteoclasts (OC) are myeloid cells of the innate immune system and are considered to play a central role in the inflammatory and destructive events of arthritis by production of inflammatory cytokines and mediating pathological bone resorption. In recent years, the use of novel fate mapping strategies identifying the origin and cellular development (ontogeny) of OC and macrophages in conjunction with new genetically modified mouse models, single cell analysis and advanced imaging techniques substantially changed our understanding on the ontogenetic and functional heterogeneity of these cells.

scholarly journals Single-Cell Analysis of the Human T Regulatory Population Uncovers Functional Heterogeneity and Instability within FOXP3+ Cells

2011 ◽  
Vol 186 (12) ◽  
pp. 6788-6797 ◽  
Author(s):  
Eva d’Hennezel ◽  
Ekaterina Yurchenko ◽  
Evridiki Sgouroudis ◽  
Valérie Hay ◽  
Ciriaco A. Piccirillo
Keyword(s):  
Single Cell ◽  
Single Cell Analysis ◽  
Cell Analysis ◽  
Functional Heterogeneity

Abstract A101: Single-cell analysis reveals the pivotal role of the innate immune compartment in aCTLA-4 antitumor response

2020 ◽  
Author(s):  
Ido Yofe ◽  
Adam Jelinski ◽  
Isabelle Solomon ◽  
Tomer Landsberger ◽  
Marc Robert de Massy ◽  
...  
Keyword(s):  
Single Cell ◽  
Single Cell Analysis ◽  
Innate Immune ◽  
Pivotal Role ◽  
Cell Analysis ◽  
Antitumor Response

scholarly journals Combinational clustering of receptors following stimulation by bacterial products determines lipopolysaccharide responses

2004 ◽  
Vol 381 (2) ◽  
pp. 527-536 ◽  
Author(s):  
Martha TRIANTAFILOU ◽  
Klaus BRANDENBURG ◽  
Shoichi KUSUMOTO ◽  
Koichi FUKASE ◽  
Alan MACKIE ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Innate Immune System ◽  
Imaging Techniques ◽  
Innate Immune ◽  
Surface Receptors ◽  
Wide Range ◽  
Species Specific ◽  
Receptor Clusters ◽  
Molecular Patterns

The innate immune system has the capacity to recognize a wide range of pathogens based on conserved PAMPs (pathogen-associated molecular patterns). In the case of bacterial LPS (lipopolysaccharide) recognition, the best studied PAMP, it has been shown that the innate immune system employs at least three cell-surface receptors: CD14, TLR4 (Toll-like receptor 4) and MD-2 protein. CD14 binds LPS from Enterobacteriaceae and then transfers it to MD-2, leading to TLR4 aggregation and signal transduction. LPS analogues such as lipid IVa seem to act as LPS antagonists in human cells, but exhibit LPS mimetic activity in mouse cells. Although TLR4 has been shown to be involved in this species-specific discrimination, the mechanism by which this is achieved has not been elucidated. The questions that remain are how the innate immune system can discriminate between LPS from different bacteria as well as different LPS analogues, and whether or not the structure of LPS affects its interaction with the CD14–TLR4–MD-2 cluster. Is it possible that the ‘shape’ of LPS induces the formation of different receptor clusters, and thus a different immune response? In the present study, we demonstrate using biochemical as well as fluorescence-imaging techniques that different LPS analogues trigger the recruitment of different receptors within microdomains. The composition of each receptor cluster as well as the number of TLR4 molecules that are recruited within the cluster seem to determine whether an immune response will be induced or inhibited.

scholarly journals A Computational Modeling Framework to Analyze Synovial-Tissue Based Drug Targets and Diagnostic Biomarkers in Rheumatoid Arthritis

2021 ◽  
Author(s):  
Paridhi Latawa ◽  
Brianna Chrisman
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Tissue ◽  
Drug Targets ◽  
Bone Erosion ◽  
Cartilage Destruction ◽  
Modeling Framework ◽  
Diagnostic Biomarkers ◽  
Number Of Patients ◽  
Targeted Treatments ◽  
Inflammatory Autoimmune Disease

Rheumatoid Arthritis (RA) is an inflammatory autoimmune disease that affects 23 million people worldwide. It is a clinically heterogeneous disorder characterized by the attack of inflammatory chemicals on the synovial tissue that lines joints. It is advantageous to develop effective, targeted treatments and identify specific diagnostic biomarkers for RA before extensive joint degradation, bone erosion, and cartilage destruction. Current modes of RA treatments have alleviated and notably halted the progression of RA. Despite this, not many patients reach low disease activity status after treatment, and a significant number of patients fail to respond to medication due to drug non-specificity. While the reasons for these rates remain unknown, the cellular and molecular signatures present in the synovial tissue for RA patients likely play a role in the varied treatment response. Thus, a drug that particularly targets specific genes and networks may have a significant effect in halting the progression of RA. This study evaluates and proposes potential drug targets through in silico mathematical modeling of various pathways of interest in RA. To understand how drugs interact with genes, we built a mathematical model with 30 two-gene and three-gene network interactions and analyzed the effect of 92 different perturbations to rate constants. We determined that inhibition of the LCK-CD4, VAV1-CD4, and MLT-ROR pathways could potentially serve as drug targets. We also found that increased activity of the DEC2-IL1β and the NF-κB-interleukin pathway and the decreased activity of the TNF-α-REV-ERB pathway could serve as diagnostic biomarkers.

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