IFNα Impairs Autophagic Degradation of mtDNA Promoting Autoreactivity of SLE Monocytes in a STING-Dependent Fashion

Publication date: 23 October 2018Source: Cell Reports, Volume 25, Issue 4Author(s): Katerina Gkirtzimanaki, Eleni Kabrani, Dimitra Nikoleri, Alexander Polyzos, Athanasios Blanas, Prodromos Sidiropoulos, Antonis Makrigiannakis, George Bertsias, Dimitrios T. Boumpas, Panayotis VerginisSummaryInterferon α (IFNα) is a prompt and efficient orchestrator of host defense against nucleic acids but upon chronicity becomes a potent mediator of autoimmunity. Sustained IFNα signaling is linked to pathogenesis of systemic lupus erythematosus (SLE), an incurable autoimmune disease characterized by aberrant self-DNA sensing that culminates in anti-DNA autoantibody-mediated pathology. IFNα instructs monocytes differentiation into autoinflammatory dendritic cells (DCs) than potentiates the survival and expansion of autoreactive lymphocytes, but the molecular mechanism bridging sterile IFNα-danger alarm with adaptive response against self-DNA remains elusive. Herein, we demonstrate IFNα-mediated deregulation of mitochondrial metabolism and impairment of autophagic degradation, leading to cytosolic accumulation of mtDNA that is sensed via stimulator of interferon genes (STING) to promote induction of autoinflammatory DCs. Identification of mtDNA as a cell-autonomous enhancer of IFNα signaling underlines the significance of efficient mitochondrial recycling in the maintenance of peripheral tolerance. Antioxidant treatment and metabolic rescue of auto...
Source: Cell Reports - Category: Cytology Source Type: research

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Authors: Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR Abstract Introduction: Leukodystrophies constitute heterogenous group of rare heritable disorders primarily affecting the white matter of central nervous system. These conditions are often under-appreciated among physicians. The first clinical manifestations of leukodystrophies are often nonspecific and can occur in different ages from neonatal to late adulthood periods. The diagnosis is, therefore, challenging in most cases.Area covered: Herein, the authors discuss different aspects of leukodystrophies. The authors used...
Source: Expert Review of Neurotherapeutics - Category: Neurology Tags: Expert Rev Neurother Source Type: research
Publication date: Available online 13 December 2019Source: Brain, Behavior, and ImmunityAuthor(s): N.B. Teixeira, M.B. Sant'Anna, A.C. Giardini, L.P. Araujo, L.A. Fonseca, A.S. Basso, Y. Cury, G. PicoloAbstractMultiple sclerosis (MS) is a Central Nervous System inflammatory demyelinating disease that has as primary symptoms losses of sensory and motor functions, including chronic pain. To date, however, few studies have investigated the mechanisms of chronic pain in animal models of MS since locomotor impairments render difficult its evaluation. It was previously demonstrated that in the MOG35-55-induced EAE, an animal mod...
Source: Brain, Behavior, and Immunity - Category: Neurology Source Type: research
Publication date: Available online 12 December 2019Source: Best Practice &Research Clinical Endocrinology &MetabolismAuthor(s): Sriram Gubbi, Fady Hannah-Shmouni, Joseph G. Verbalis, Christian A. KochAbstractHypophysitis is a heterogeneous condition that leads to inflammation of the sella and/or suprasellar region, potentially resulting in hormonal deficiencies and/or mass effects. A preponderance of hypophysitis subtypes have an underlying autoimmune aetiology. The overall incidence and prevalence of hypophysitis has dramatically increased over the past decade, mainly due to increased awareness of the condition in...
Source: Best Practice and Research Clinical Endocrinology and Metabolism - Category: Endocrinology Source Type: research
Publication date: Available online 12 December 2019Source: Pharmacological ResearchAuthor(s): Jangho Lee, Ju-Yong Hyon, Jin Young Min, Yang Hoon Huh, Hyo Jung Kim, Hayoung Lee, Sung Ho Yun, Chi-Won Choi, Su Jeong Ha, Joon Park, Young-Ho Chung, Hye Gwang Jeong, Sang Keun Ha, Sung Keun Jung, YoonSook Kim, Eun Hee HanAbstractDiabetic nephropathy (DN) is the most common cause of end-stage renal disease in the world. Advanced glycation end products (AGEs) are thought to be involved in the pathogenesis of DN via multifactorial mechanisms including the generation of oxidative stress and overproduction of various growth factors an...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 12 December 2019Source: Pharmacological ResearchAuthor(s): Karan Naresh Amin, Elango Bhakkiyalakshmi, Jayasuriya Ravichandran, D.V.L. Sarada, Ramkumar Kunka MohanramAbstractEndothelial dysfunction (ED) is a key event in the onset and progression of vascular complications associated with diabetes. Regulation of endothelial function and the underlying signaling mechanisms in the progression of diabetes-induced vascular complications have been well established. Recent studies indicate that increased oxidative stress is an important determinant of endothelial injury and patients with hyperten...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research
ConclusionsBioactive constituents of the extract imbalances oxidative status of thyrocytes impairing action of hormone synthesizing elements at cellular and molecular level.Graphical abstract
Source: Journal of Ethnopharmacology - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 12 December 2019Source: Autoimmunity ReviewsAuthor(s): Dennis McGonagle, Nicola Luigi Bragazzi, Howard Amital, Abdulla WatadAbstractImproved anti-tumour responses under immune checkpoint inhibition (ICI) are associated with concomitant autoimmune disease development termed immune related adverse events (irAEs), of which approximately 5% are rheumatic in nature. Generally, oncologists and other specialists vigorously treat irAEs in spite of the generally accepted beneficial effect of irAEs on tumour survival. Herein, we highlight mechanistic insights on how tumour responses and certain typ...
Source: Autoimmunity Reviews - Category: Allergy & Immunology Source Type: research
ConclusionsIPAF seems to a distinct entity, with a low tendency to evolve in a definite CTD. Nevertheless, further studies are needed to better define the clinical evolution and the outcome of IPAF.
Source: Autoimmunity Reviews - Category: Allergy & Immunology Source Type: research
Publication date: Available online 12 December 2019Source: Autoimmunity ReviewsAuthor(s): Ruth Percik, Gadi Shlomai, Amir Tirosh, Amit Tirosh, Raya Leibowitz-Amit, Yael Eshet, Gahl Greenberg, Alex Merlinsky, Ehud Barhod, Yael Steinberg-Silman, Tal SellaAbstractObjectiveImmune checkpoint inhibitors have introduced a new and heterogeneous class of immune-related adverse effects, with the endocrine system being a predominant target for autoimmunity. Autoimmune hypothalamic-pituitary-adrenal axis (HPA) diseases induced by checkpoint inhibitors are being increasingly recognized. We aimed to characterize the spectrum of checkpoi...
Source: Autoimmunity Reviews - Category: Allergy & Immunology Source Type: research
In conclusion, a polypharmacology approach of combining established, prolongevity drug inhibitors of specific nodes may be the most effective way to target the nutrient-sensing network to improve late-life health. Deletion of p38α in Neurons Slows Neural Stem Cell Decline and Loss of Cognitive Function in Mice https://www.fightaging.org/archives/2019/10/deletion-of-p38%ce%b1-in-neurons-slows-neural-stem-cell-decline-and-loss-of-cognitive-function-in-mice/ Researchers here provide evidence for p38α to be involved in the regulation of diminished neural stem cell activity with age. It is thought...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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