0000000000939460
AUTHOR
Nigil Haroon
OP0204 Autophagy and Unfolded Protein Response: A Fine Balance that can Influence the Pathogenesis of Ankylosing Spondylitis and Inflammatory Bowel Disease
Background We have shown an increase in the unfolded protein response (UPR) with decreased ERAP1 or ERAP2 function in an in vitro system. Similarly UPR has been demonstrated to correlate with onset of disease in the HLA-B27 rat model. UPR has been difficult to demonstrate in the gut of AS patients but autophagy is upregulated. ERAP2 is associated with both AS and inflammatory bowel disease (IBD). Objectives Here we explore the moderating effect of autophagy on UPR. Specifically we study the impact of suppressing autophagy on UPR. Methods Lamina Propria Mononuclear cells (LPMC) were isolated from terminal ileal biopsies of 10 AS patients. Autophagy was suppressed with 2 agents anisomycin and…
Pro-inflammatory CX3CR1+ CD59+ TL1A+ IL-23+ monocytes are expanded in patients with Ankylosing Spondylitis and modulate ILC3 immune functions
Gut derived ILC3 have been demonstrated to participate in AS pathogenesis. CX3CR1+ mononuclear phagocytes (MNP) have been demonstrated to modulate ILC3 function in the gut. The aim of this study was to study the role of pro-inflammatory CX3CR1+ CD59+ MNP in modulating ILC3 function in AS patients.
Autophagy in the pathogenesis of ankylosing spondylitis
The pathogenesis of ankylosing spondylitis (AS) is not well understood, and treatment options have met with limited success. Autophagy is a highly conserved mechanism of controlled digestion of damaged organelles within a cell. It helps in the maintenance of cellular homeostasis. The process of autophagy requires the formation of an isolation membrane. They form double-membraned vesicles called “autophagosomes” that engulf a portion of the cytoplasm. Beyond the role in maintenance of cellular homeostasis, autophagy has been demonstrated as one of the most remarkable tools employed by the host cellular defense against bacteria invasion. Autophagy also affects the immune system and thus is im…
Macrophage Migration Inhibitory Factor Induces Inflammation and Predicts Spinal Progression in Ankylosing Spondylitis
Objectives: To understand the role of macrophage migration inhibitory factor (MIF) in the pathogenesis of Ankylosing Spondylitis (AS). Methods: AS patients satisfying the modified New York criteria were recruited for the study. Healthy volunteers, rheumatoid arthritis and osteoarthritis patients were included as controls. Based on the annual rate of increase in mSASSS scores, AS patients were classified as progressors or non-progressors. MIF levels were quantitated by ELISA in the serum and synovial fluid. Predictors of AS progression were studied by logistic regression analysis. Immunohistochemistry of ileal tissue was performed to identify MIF producing cells. Flow cytometry was used to r…
Macrophage Migration Inhibitory Factor Induces Inflammation and Predicts Spinal Progression in Ankylosing Spondylitis
Objective: To investigate the role of macrophage migration inhibitory factor (MIF) in the pathogenesis of ankylosing spondylitis (AS). Methods: Patients who met the modified New York criteria for AS were recruited for the study. Healthy volunteers, rheumatoid arthritis patients, and osteoarthritis patients were included as controls. Based on the annual rate of increase in modified Stoke AS Spine Score (mSASSS), AS patients were classified as progressors or nonprogressors. MIF levels in serum and synovial fluid were quantitated by enzyme-linked immunosorbent assay. Predictors of AS progression were evaluated using logistic regression analysis. Immunohistochemical analysis of ileal tissue was…
Proinflammatory CX3CR1+CD59+Tumor Necrosis Factor–Like Molecule 1A+Interleukin‐23+ Monocytes Are Expanded in Patients With Ankylosing Spondylitis and Modulate Innate Lymphoid Cell 3 Immune Functions
Objective: Gut-derived innate lymphoid cell 3 (ILC3) has been shown to participate in the pathogenesis of ankylosing spondylitis (AS). CX3CR1+ mononuclear phagocytes (MNPs) have been demonstrated to modulate ILC3 function in the gut. This study was undertaken to investigate the role of proinflammatory CX3CR1+CD59+ MNPs in modulating ILC3 function in AS patients. Methods: MNP subsets in the blood of AS patients and controls were analyzed by flow cytometry. The presence of CX3CR1+CD59+ cells in tissue was confirmed by confocal microscopy. Expression of the proinflammatory chemokines CX3CL1 and CCL2 and decoy receptor 6 (DcR-6) was analyzed. Peripheral CX3CR1+CD59+ cells were cocultured with I…
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1
Contains fulltext : 232759.pdf (Publisher’s version ) (Closed access) In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to…
Autophagy
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide…