The Bidirectional Relationship of Depression and Inflammation: Double Trouble

Neuron, Journal Year: 2020, Volume and Issue: 107(2), P. 234 - 256

Published: June 17, 2020

Language: Английский

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Single-Cell Mapping of Human Brain Cancer Reveals Tumor-Specific Instruction of Tissue-Invading Leukocytes

Cell, Journal Year: 2020, Volume and Issue: 181(7), P. 1626 - 1642.e20

Published: May 28, 2020

Language: Английский

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RANKL biology: bone metabolism, the immune system, and beyond

Inflammation and Regeneration, Journal Year: 2020, Volume and Issue: 40(1)

Published: Feb. 7, 2020

Abstract Receptor activator of NF-κB (RANK) ligand (RANKL) induces the differentiation monocyte/macrophage–lineage cells into bone–resorbing called osteoclasts. Because abnormalities in RANKL, its signaling receptor RANK, or decoy osteoprotegerin (OPG) lead to bone diseases such as osteopetrosis, RANKL/RANK/OPG system is essential for resorption. RANKL was first discovered a T cell-derived dendritic (DCs) and has many functions immune system, including organogenesis, cellular development. The essentiality systems lies at root field “osteoimmunology.” Furthermore, this cytokine beyond domains metabolism e.g., mammary gland hair follicle formation, body temperature regulation, muscle metabolism, tumor In review, we will summarize current understanding biological processes.

Language: Английский

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Therapeutic AAV Gene Transfer to the Nervous System: A Clinical Reality

Neuron, Journal Year: 2019, Volume and Issue: 101(5), P. 839 - 862

Published: March 1, 2019

Language: Английский

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Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters

Brain Behavior and Immunity, Journal Year: 2020, Volume and Issue: 89, P. 579 - 586

Published: July 3, 2020

Language: Английский

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The Role of Inflammation in Diabetic Retinopathy

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Nov. 6, 2020

Inflammation is central to pathogenic processes in diabetes mellitus and the metabolic syndrome particularly implicates innate immunity development of complications. a primary event Type 1 where infectious (viral) / or autoimmune initiate disease; contrast, chronic inflammation typical 2 considered sequel increasing insulin resistance disturbed glucose metabolism. Diabetic retinopathy (DR) perceived as vascular neurodegenerative disease which occurs after some years poorly controlled diabetes. However, many clinical features DR are late events reflect nature retinal architecture its cellular composition. Retinal microvascular is, fact, an early pathogenetically, induced by low grade, persistent leukocyte activation causes repeated episodes capillary occlusion and, progressive, attritional ischemia. The later, overt signs consequence Metabolic dysregulation involving both lipid metabolism may lead activation. On molecular level, we have shown that macrophage-restricted protein tyrosine phosphatase 1B (PTP1B) key regulator it possible PTP1B underlie disease. We also adherent CCR5+CD11b+ monocyte macrophages appear be selectively involved occlusion. In this review, discuss relationship between later DR, common pathogenetic diabetic other retinopathies, mechanisms whereby hyperglycemia dyslipidemia, signaling disease, interventions prevent these retinopathies. address role for adaptive DR. Although significant improvements treatment been made with intravitreal anti-VEGF therapy, sizeable proportion patients, sight-threatening macular edema, fail respond. Alternative therapies targeting inflammatory offer advantage.

Language: Английский

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Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2020, Volume and Issue: unknown

Published: April 20, 2020

ABSTRACT The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, creates an urgent need for identifying molecular mechanisms that mediate viral entry, propagation, and tissue pathology. Cell membrane bound angiotensin-converting enzyme 2 (ACE2) associated proteases, transmembrane protease serine (TMPRSS2) Cathepsin L (CTSL), were previously identified as mediators of SARS-CoV2 cellular entry. Here, we assess cell type-specific RNA expression ACE2 , TMPRSS2 CTSL through integrated analysis 107 single-cell single-nucleus RNA-Seq studies, including 22 lung airways datasets (16 unpublished), 85 from other diverse organs. Joint accessory proteases identifies specific subsets respiratory epithelial cells putative targets infection in nasal passages, airways, alveoli. Cells co-express are also organs, some which have been with transmission or pathology, gut enterocytes, corneal cells, cardiomyocytes, heart pericytes, olfactory sustentacular renal cells. Performing first meta-analyses scRNA-seq analyzed 1,176,683 282 nasal, airway, parenchyma samples 164 donors spanning fetal, childhood, adult, elderly age groups, associate increased levels types increasing age, male gender, smoking, all epidemiologically linked to susceptibility outcomes. Notably, there was a particularly low few young pediatric analysis. Further reveals gene program shared + tissues, genes may subtend key immune functions, epithelial-macrophage cross-talk. Amongst these IL6, its receptor co-receptor, IL1R TNF response pathways, complement genes. type specificity smoking effects conserved mice. Our analyses suggest differences SARS-CoV-2 entry be responsible aspects epidemiology clinical course, point pathways involved disease pathogenesis.

Language: Английский

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A single-cell atlas of the normal and malformed human brain vasculature

Science, Journal Year: 2022, Volume and Issue: 375(6584)

Published: Jan. 27, 2022

Cerebrovascular diseases are a leading cause of death and neurologic disability. Further understanding disease mechanisms therapeutic strategies requires deeper knowledge cerebrovascular cells in humans. We profiled transcriptomes 181,388 to define cell atlas the adult human cerebrovasculature, including endothelial molecular signatures with arteriovenous segmentation expanded perivascular diversity. By leveraging this reference, we investigated cellular perturbations brain malformations, which stroke young people, identified pathologic transformations abnormal vascular patterning ontology vascularly derived inflammation. illustrate interplay between immune that contributes hemorrhage catalog opportunities for targeting angiogenic inflammatory programs malformations.

Language: Английский

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Hair follicle immune privilege and its collapse in alopecia areata

Experimental Dermatology, Journal Year: 2020, Volume and Issue: 29(8), P. 703 - 725

Published: July 18, 2020

Anagen stage hair follicles (HFs) exhibit "immune privilege (IP)" from the level of bulge downwards to bulb. Both passive and active IP mechanisms protect HFs physiologically undesired immune responses limit surveillance. is relative, not absolute, primarily based on absent, or greatly reduced, intra-follicular antigen presentation via MHC class I II molecules, along with prominent expression "no danger" signals like CD200 creation an immunoinhibitory signalling milieu generated by secretory activities HFs. Perifollicular mast cells, Tregs other immunocytes may also contribute HF maintenance in healthy human skin. Collapse anagen bulb essential prerequisite for development alopecia areata (AA). In AA, lesional are rapidly infiltrated NKG2D + T cells natural killer (NK) while perifollicular acquire a profoundly pro-inflammatory phenotype interact autoreactive CD8+ cells. Using animal models, significant functional evidence has accumulated that demonstrates dominance system AA pathogenesis. Purified CD8+T-cell NK cell populations alone, which secrete fγ, suffice induce phenotype, CD4+T-cells aggravate it, iNKT provide relative protection against development. While collapse be induced exogenous agents, inherent deficiencies might confer increased susceptibility some individuals. Thus, key goal effective management re-establishment IP, will superior disease relapse.

Language: Английский

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Toxoplasma gondii infection and its implications within the central nervous system

Nature Reviews Microbiology, Journal Year: 2021, Volume and Issue: 19(7), P. 467 - 480

Published: Feb. 24, 2021

Language: Английский

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