scholarly journals Macrophages inhibit and enhance endometriosis depending on their origin

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.

scholarly journals Macrophages inhibit and enhance endometriosis depending on their origin

2021 ◽  
Vol 118 (6) ◽  
pp. e2013776118 ◽  
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.

scholarly journals Profiling Non-Coding RNA Levels With Clinical Classifiers in Pediatric Crohn’s Disease

2020 ◽  
Author(s):  
Ranjit S. Pelia ◽  
Suresh Venkateswaran ◽  
Jason D. Matthews ◽  
Yael Haberman ◽  
David J. Cutler ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Progression ◽  
Protein Function ◽  
Inflammatory Disorder ◽  
Substantial Impact ◽  
Chronic Inflammatory Disorder ◽  
Inflammatory Status ◽  
Disease Behavior ◽  
Non Coding Rnas

Abstract Background: Crohn’s disease (CD) is a heritable chronic inflammatory disorder. Non-coding RNAs (ncRNAs) play an important role in epigenetic regulation by affecting gene expression, but can also directly affect protein function, thus having a substantial impact on biological processes. We investigated whether non-coding RNAs (ncRNA) at diagnosis are dysregulated during CD at different CD locations and future disease behaviors to determine if ncRNA signatures can serve as an index to outcomes. Methods: Using subjects belonging to the RISK cohort, we analyzed ncRNA from the ileal biopsies of 345 CD and 71 non-IBD controls, and ncRNA from rectal biopsies of 329 CD and 61 non-IBD controls. Sequence alignment was done (STAR package) using Human Genome version 38 (hg38) as reference panel. The differential expression (DE) analysis was performed with EdgeR package and DE ncRNAs were identified with a threshold of fold change (FC) >2 and FDR < 0.05 after multiple test corrections. Results: In total, we identified 130 CD specific DE ncRNAs (89 in ileum and 41 in rectum) when compared to non-IBD controls. Similarly, 35 DE ncRNAs were identified between B1 and B2 in ileum, whereas no differences among CD disease behaviors were noticed in rectum. We also found inflammation specific ncRNAs between inflamed and non-inflamed groups in ileal biopsies. Overall, we observed that expression of mir1244-2, mir1244-3, mir1244-4, and RN7SL2 were increased during CD, regardless of disease behavior, location, or inflammatory status. Lastly, we tested ncRNA expression at baseline as potential tool to predict the disease status, disease behaviors and disease inflammation at 3-year follow up.Conclusions: We have identified ncRNAs that are specific to disease location, disease behavior, and disease inflammation in CD. Both ileal and rectal specific ncRNA are changing over the course of CD, specifically during the disease progression in the intestinal mucosa. Collectively, our findings show changes in ncRNA during CD and may have a clinical utility in early identification and characterization of disease progression.

scholarly journals Pathogenesis of polymyalgia rheumatica

Reumatismo ◽  
2018 ◽  
Vol 70 (1) ◽  
pp. 10 ◽  
Author(s):  
G. Guggino ◽  
A. Ferrante ◽  
F. Macaluso ◽  
G. Triolo ◽  
F. Ciccia
Keyword(s):  
Polymyalgia Rheumatica ◽  
Treg Cells ◽  
Inflammatory Disorder ◽  
Infectious Agents ◽  
Chronic Inflammatory Disorder ◽  
Adaptive Immune ◽  
Age Related ◽  
Immune Alterations ◽  
And Function ◽  
Adaptive Immune Systems

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.

scholarly journals Recruited macrophages that colonise the post-inflammatory peritoneal niche convert into functionally divergent resident cells

2020 ◽  
Author(s):  
P. A. Louwe ◽  
L. Badiola Gomez ◽  
H. Webster ◽  
G. Perona-Wright ◽  
C. C. Bain ◽  
...  
Keyword(s):  
Peritoneal Macrophage ◽  
Peritoneal Cavity ◽  
Peritoneal Macrophages ◽  
Environment Changes ◽  
Severe Inflammation ◽  
Progressive Loss ◽  
Independent Features ◽  
And Function ◽  
B1 Cells

AbstractInflammation generally leads to substantial recruitment of monocyte-derived macrophages. What regulates the fate of these cells and to what extent they can assume the identity and function of resident macrophages remains unclear. We compared the normal fate of inflammation-elicited macrophages in the peritoneal cavity with their potential under non-inflamed conditions and in the absence of established resident macrophages. Following mild inflammation, elicited macrophages persisted for at least 5 months but failed to fully assume a GATA6hi resident identity due to the presence of enduring resident cells. In contrast, severe inflammation resulted in ablation of resident macrophages and a protracted phase wherein the cavity was incapable of sustaining a resident phenotype, yet ultimately elicited cells acquired a mature GATA6hi identity. Elicited macrophages also exhibited divergent features resulting from inflammation-driven alterations to the peritoneal cavity micro-environment and environment-independent features related to origin and time-of-residency. Critically, one environment-dependent feature of inflammation-elicited macrophages irrespective of severity of inflammation was a failure to produce the chemokine CXCL13, which correlated with a progressive loss in accumulation of peritoneal B1 cells post-inflammation. Hence, rather than being predetermined, the fate of inflammation-elicited peritoneal macrophages appears largely regulated by environment, changes in which result in long-term alteration in function of the peritoneal macrophage compartment post-inflammation.

scholarly journals Profiling non-coding RNA levels with clinical classifiers in pediatric Crohn’s disease

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Ranjit Pelia ◽  
Suresh Venkateswaran ◽  
Jason D. Matthews ◽  
Yael Haberman ◽  
David J. Cutler ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Progression ◽  
Protein Function ◽  
Inflammatory Disorder ◽  
Substantial Impact ◽  
Chronic Inflammatory Disorder ◽  
Inflammatory Status ◽  
Disease Behavior ◽  
Non Coding Rnas

Abstract Background Crohn’s disease (CD) is a heritable chronic inflammatory disorder. Non-coding RNAs (ncRNAs) play an important role in epigenetic regulation by affecting gene expression, but can also directly affect protein function, thus having a substantial impact on biological processes. We investigated whether non-coding RNAs (ncRNA) at diagnosis are dysregulated during CD at different CD locations and future disease behaviors to determine if ncRNA signatures can serve as an index to outcomes. Methods Using subjects belonging to the RISK cohort, we analyzed ncRNA from the ileal biopsies of 345 CD and 71 non-IBD controls, and ncRNA from rectal biopsies of 329 CD and 61 non-IBD controls. Sequence alignment was done (STAR package) using Human Genome version 38 (hg38) as reference panel. The differential expression (DE) analysis was performed with EdgeR package and DE ncRNAs were identified with a threshold of fold change (FC) > 2 and FDR < 0.05 after multiple test corrections. Results In total, we identified 130 CD specific DE ncRNAs (89 in ileum and 41 in rectum) when compared to non-IBD controls. Similarly, 35 DE ncRNAs were identified between B1 and B2 in ileum, whereas no differences among CD disease behaviors were noticed in rectum. We also found inflammation specific ncRNAs between inflamed and non-inflamed groups in ileal biopsies. Overall, we observed that expression of mir1244-2, mir1244-3, mir1244-4, and RN7SL2 were increased during CD, regardless of disease behavior, location, or inflammatory status. Lastly, we tested ncRNA expression at baseline as potential tool to predict the disease status, disease behaviors and disease inflammation at 3-year follow up. Conclusions We have identified ncRNAs that are specific to disease location, disease behavior, and disease inflammation in CD. Both ileal and rectal specific ncRNA are changing over the course of CD, specifically during the disease progression in the intestinal mucosa. Collectively, our findings show changes in ncRNA during CD and may have a clinical utility in early identification and characterization of disease progression.

scholarly journals Redox Imbalance in T Cell-Mediated Skin Diseases

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Saveria Pastore ◽  
Liudmila Korkina
Keyword(s):  
Oxidative Stress ◽  
Atopic Dermatitis ◽  
Contact Dermatitis ◽  
Skin Diseases ◽  
Redox Balance ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Physical Chemical ◽  
Chemical Oxidants ◽  
Beneficial Outcome

The skin is permanently exposed to physical, chemical, and biological aggression by the environment. In addition, acute and chronic inflammatory events taking place in the skin are accompanied by abnormal release of pro-oxidative mediators. In this paper, we will briefly overview the homeostatic systems active in the skin to maintain the redox balance and also to counteract abnormal oxidative stress. We will concentrate on the evidence that a local and/or systemic redox dysregulation accompanies the chronic inflammatory disorder events associated to psoriasis, contact dermatitis, and atopic dermatitis. We will also discuss the fact that several well-established treatments for the therapy of chronic inflammatory skin disorders are based on the application of strong physical or chemical oxidants onto the skin, indicating that, in selected conditions, a further increase of the oxidative imbalance may lead to a beneficial outcome.

scholarly journals Macro- and microtranscriptomic evidence of the monocyte recruitment to regenerating liver after partial hepatectomy in mouse model

2021 ◽  
Vol 138 ◽  
pp. 111516
Author(s):  
Andrey Elchaninov ◽  
Maria Nikitina ◽  
Polina Vishnyakova ◽  
Anastasia Lokhonina ◽  
Andrey Makarov ◽  
...  
Keyword(s):  
Mouse Model ◽  
Partial Hepatectomy ◽  
Regenerating Liver ◽  
Monocyte Recruitment

scholarly journals Breeder Diet Strategies for Generating Ttpa-Null and Wild-Type Mice with Low Vitamin E Status to Assess Neurological Outcomes

2020 ◽  
Vol 4 (11) ◽  
Author(s):  
Katherine M Ranard ◽  
Matthew J Kuchan ◽  
John W Erdman
Keyword(s):  
Animal Model ◽  
Vitamin E ◽  
Mouse Model ◽  
Wild Type ◽  
Future Studies ◽  
Neurological Outcomes ◽  
Transfer Protein ◽  
And Function ◽  
The Brain ◽  
Vitamin E Status

ABSTRACT Studying vitamin E [α-tocopherol (α-T)] metabolism and function in the brain and other tissues requires an animal model with low α-T status, such as the transgenic α-T transfer protein (Ttpa)–null (Ttpa−/−) mouse model. Ttpa+/− dams can be used to produce Ttpa−/− and Ttpa+/+mice for these studies. However, the α-T content in Ttpa+/− dams’ diet requires optimization; diets must provide sufficient α-T for reproduction, while minimizing the transfer of α-T to the offspring destined for future studies that require low baseline α-T status. The goal of this work was to assess the effectiveness and feasibility of 2 breeding diet strategies on reproduction outcomes and offspring brain α-T concentrations. These findings will help standardize the breeding methodology used to generate the Ttpa−/− mice for neurological studies.

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