Extracellular Chromatin Triggers Release of Soluble CEACAM8 Upon Activation of Neutrophils

Increased concentrations of extracellular chromatin are observed in cancer, sepsis and inflammatory autoimmune diseases like systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). In SLE and RA, extracellular chromatin may behave as a danger-associated molecular pattern (DAMP). Polymorphonuclear neutrophils (PMN) are described as typical pro-inflammatory cells but possess also immunoregulatory properties. They are activated in SLE and RA but surprisingly remain moderately studied in these diseases, and especially the disease-associated stimuli triggering PMN activation are still not completely characterized. PMN express plasma membrane carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 8 (CD66b) and secrete a soluble form of CEACAM8 after activation. Soluble CEACAM8 has in turn immunoregulatory functions. However, few natural stimuli inducing soluble CEACAM8 secretion by PMN have been identified. Here we demonstrate for the first time that extracellular chromatin triggers secretion of soluble CEACAM8 by primary human PMN. Priming of PMN was not required. Secretion was associated with activation of PMN. Similar induction of soluble CEACAM8 release was observed with purified mono-nucleosomes as well as long chromatin fragments and occurred in a time-dependent and concentration-dependent manner. Results indicate that chromatin induces both neo-synthesis of soluble CEACAM8 and release of soluble CEACAM8 through degranulation. In addition, we report the pre...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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Purpose: To evaluate the infection incidence in breast cancer patients whether they have a major autoimmune disease or not.Methods: This retrospective cohort study compared the infection incidence of 174 breast cancer patients with an autoimmune disease, including Sjogren's Syndrome (SS), Rheumatoid Arthritis (RA), and Systemic Lupus Erythematosus (SLE), along with 4429 patients without an autoimmune disease, for the period 2000 to 2016. Six-hundred and ninety six, age-, stage-, and diagnosis era-matched patients without any autoimmune disease were analyzed to eliminate the effects of these confounding factors may have on ...
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
AbstractIn the vast database of peer-reviewed articles, the number of 2018 papers published retrieved using the “autoimmunity” keyword remained unchanged compared with the brilliant results of 2017 while returning above a 5% share within the immunology field, after the brisk decrease of this ratio in 2017. As in the past 12 years, we have now searched PubMed for publications related to autoimmunity in th e major immunology and autoimmunity peer-reviewed journals and provide here an arbitrary discussion of the major themes encountered. Once again, we are happy to notice that similarities between autoimmune ...
Source: Clinical Reviews in Allergy and Immunology - Category: Allergy & Immunology Source Type: research
In this study, we analyzed the metabolic profiling of fecal samples from SLE patients and healthy controls based on ultra-high-performance liquid chromatography equipped with mass spectrometry for exploring the potential biomarkers of SLE. The results showed that 23 differential metabolites and 5 perturbed pathways were identified between the two groups, including aminoacyl-tRNA biosynthesis, thiamine metabolism, nitrogen metabolism, tryptophan metabolism, and cyanoamino acid metabolism. In addition, logistic regression and ROC analysis were used to establish a diagnostic model for distinguishing SLE patients from healthy ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions The clinical trials discussed here, which include several trials investigating novel therapeutic targets, demonstrate that translational research in pemphigus and pemphigoid is a fast-growing field. We thus expect that several novel treatments will be shortly available for the treatment of pemphigus and pemphigoid patients. Given the high, and thus far unmet, medical need in this field (110), this is highly encouraging and will hopefully improve the quality of life of the affected patients. In addition to the compounds and targets described here, several new targets have been recently identified in preclinical...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Discussion MDSCs violently emerge in pathological conditions in an attempt to limit potentially harmful immune and inflammatory responses. Mechanisms supporting their expansion and survival are deeply investigated in cancer, in the perspective to reactivate specific antitumor responses and prevent their contribution to disease evolution. These findings will likely contribute to improve the targeting of MDSCs in anticancer immunotherapies, either alone or in combination with immune checkpoint inhibitors. New evidence indicates that the expansion of myeloid cell differentiation in pathology is subject to fine-tuning, as its...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Gulcin Tezcan1, Ekaterina V. Martynova1, Zarema E. Gilazieva1, Alan McIntyre2, Albert A. Rizvanov1 and Svetlana F. Khaiboullina1,3* 1Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia 2Centre for Cancer Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, United Kingdom 3Department of Microbiology and Immunology, University of Nevada, Reno, Reno, NV, United States Inflammation has a crucial role in protection against various pathogens. The inflammasome is an intracellular multiprotein signaling complex that is linked to pathogen sensing and...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
In this study, we therefore examined whether FKN could stimulate the process of EMT, NF-kB, TGFβ, CCL22, F4/80, inflammation, and tubulointerstitial fibrosis in a murine model of LN. We also determined whether FKN was involved in the EMT process of Wnt/β-catenin-expressing HK-2 cells. Mechanistically, we ascertained, for the first time, whether FKN up-regulated EMT-related gene signatures (e.g., vimentin, α-SMA), and hence, renal tubulointerstitial fibrogenesis, and the role of the Wnt/β-catenin signaling pathway in this process. Materials and Methods Cell Culture, Stable Infection, and Grouping HK-...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Maunil K. Desai1 and Roberta Diaz Brinton2,3* 1School of Pharmacy, University of Southern California, Los Angeles, CA, United States 2Center for Innovation in Brain Science, University of Arizona, Tucson, AZ, United States 3Departments of Pharmacology and Neurology, College of Medicine, University of Arizona, Tucson, AZ, United States Women have a higher incidence and prevalence of autoimmune diseases than men, and 85% or more patients of multiple autoimmune diseases are female. Women undergo sweeping endocrinological changes at least twice during their lifetime, puberty and menopause, with many women undergoin...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
Conclusion: Our data indicate reduced P2X7R expression and function in SLE patients compared with HC and, conversely, increased IL-6 signaling. The possible consequences of reduced P2X7R, mainly on cytokines network deregulation and lymphocyte proliferation, will be further investigated as well as the role of IL-6 as a possible therapeutic target especially in lupus serositis. Introduction With the first reports of Burnstock in 1970s, adenosine triphosphate (ATP) has passed from a simple molecule devoted to energy reserve, to a relevant extracellular signaling molecule able to mediate numerous physiological and pat...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Laura Stronati1, Francesca Palone2, Anna Negroni3, Eleonora Colantoni2, Anna Barbara Mancuso2, Salvatore Cucchiara2, Vincenzo Cesi3, Sara Isoldi2 and Roberta Vitali3* 1Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy 2Pediatric Gastroenterology and Liver Unit, Department of Pediatrics, Sapienza University of Rome, Rome, Italy 3Division of Health Protection Technologies, Territorial and Production Systems Sustainability Department, ENEA, Rome, Italy Gut mucosal healing (MH) is considered a key therapeutic target and prognostic parameter in the management of inflammatory bowel disease (I...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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