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Daria Esterházy et al.
Nature, 569(7754), 126-130 (2019-04-17)
The intestinal immune system has the challenging task of tolerating foreign nutrients and the commensal microbiome, while excluding or eliminating ingested pathogens. Failure of this balance leads to conditions such as inflammatory bowel diseases, food allergies and invasive gastrointestinal infections1.
Bianca B Jütte et al.
iScience, 24(8), 102833-102833 (2021-08-10)
Intercellular transmission of the second messenger 2',3'-cGAMP, synthesized by the viral DNA sensor cGAMP synthase (cGAS), is a potent mode of bystander activation during host defense. However, whether this mechanism also contributes to cGAS-dependent autoimmunity remains unknown. Here, using a
Surbhi Khurana et al.
Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine, 24(11), 1037-1044 (2021-01-02)
One of the leading causes of morbidity and early-age mortality across the globe is trauma. It disrupts immune system homeostasis and intensely affects the innate and adaptive immune responses, predisposing patients to posttrauma complications and poor outcomes. Most of the
Li Zheng et al.
Biomolecules, 10(10) (2020-10-22)
The autosomal-dominant pleiotropic disorder called oculodentodigital dysplasia (ODDD) is caused by mutations in the gap junction protein Cx43. Of the 73 mutations identified to date, over one-third are localized in the cytoplasmic loop (Cx43CL) domain. Here, we determined the mechanism
Peter Jan Hooikaas et al.
eLife, 9 (2020-12-22)
When a T cell and an antigen-presenting cell form an immunological synapse, rapid dynein-driven translocation of the centrosome toward the contact site leads to reorganization of microtubules and associated organelles. Currently, little is known about how the regulation of microtubule
Wei Qian et al.
Journal of virology, 93(19) (2019-07-19)
Autosomal dominant STAT1 mutations in humans have been associated with chronic mucocutaneous candidiasis (CMC), as well as with increased susceptibility to herpesvirus infections. Prior studies have focused on mucosal and Th17-mediated immunity against Candida, but mechanisms of impaired antiviral immunity
Rakesh Kumar Banote et al.
Scientific reports, 10(1), 10127-10127 (2020-06-25)
Understanding the biological function of amyloid beta (Aβ) precursor protein (APP) beyond its role in Alzheimer's disease is emerging. Yet, its function during embryonic development is poorly understood. The zebrafish APP orthologue, Appb, is strongly expressed during early development but
Kathleen A Bishop et al.
The Journal of biological chemistry, 286(23), 20880-20891 (2011-04-14)
Receptor activator of NF-κB ligand (Rankl) is a TNF-like factor that induces the formation of osteoclasts responsible for bone resorption. Although T cell activation up-regulates this gene, the molecular mechanism of its transcriptional control remains unknown. We used ChIP-chip analysis
Anna Śledzińska et al.
Immunity, 52(1), 151-166 (2020-01-12)
In addition to helper and regulatory potential, CD4+ T cells also acquire cytotoxic activity marked by granzyme B (GzmB) expression and the ability to promote rejection of established tumors. Here, we examined the molecular and cellular mechanisms underpinning the differentiation of
Mu A et al.
Nature cell biology, 21(5), 592-602 (2019-04-10)
Inverted formin 2 (INF2) is a member of the formin family of actin assembly factors. Dominant missense mutations in INF2 are linked to two diseases: focal segmental glomerulosclerosis, a kidney disease, and Charcot-Marie-Tooth disease, a neuropathy. All of the disease
Annarita Favia et al.
Proceedings of the National Academy of Sciences of the United States of America, 111(44), E4706-E4715 (2014-10-22)
Vascular endothelial growth factor (VEGF) and its receptors VEGFR1/VEGFR2 play major roles in controlling angiogenesis, including vascularization of solid tumors. Here we describe a specific Ca(2+) signaling pathway linked to the VEGFR2 receptor subtype, controlling the critical angiogenic responses of
Tak Shun Fung et al.
Journal of cell science, 132(18) (2019-08-16)
Recent studies show that mitochondria and actin filaments work together in two contexts: (1) increased cytoplasmic calcium induces cytoplasmic actin polymerization that stimulates mitochondrial fission and (2) mitochondrial depolarization causes actin assembly around mitochondria, with roles in mitophagy. It is
Daniel V Lopez et al.
Frontiers in immunology, 12, 715059-715059 (2021-08-20)
Th22 cells constitute a recently described CD4+ T cell subset defined by its production of interleukin (IL)-22. The action of IL-22 is mainly restricted to epithelial cells. IL-22 enhances keratinocyte proliferation but inhibits their differentiation and maturation. Dysregulated IL-22 production
Benjamin N Ostendorf et al.
Nature medicine, 26(7), 1048-1053 (2020-05-27)
Common germline variants of the APOE gene are major risk modifiers of neurodegenerative and atherosclerotic diseases1-3, but their effect on cancer outcome is poorly defined. Here we report that, in a reversal of their effect on Alzheimer's disease, the APOE4
Diana E Matei et al.
Med (New York, N.Y.), 2(7), 864-883 (2021-07-24)
Evidence suggests an important role for gut-microbiota dysbiosis in the development of rheumatoid arthritis (RA). The link between changes in gut bacteria and the development of joint inflammation is missing. Here, we address whether there are changes to the gut
Viola L Boccasavia et al.
Cell reports, 34(11), 108861-108861 (2021-03-18)
T cells form immunological synapses with professional antigen-presenting cells (APCs) resulting in T cell activation and the acquisition of peptide antigen-MHC (pMHC) complexes from the plasma membrane of the APC. They thus become APCs themselves. We investigate the functional outcome of
Young Hwan Park et al.
Biomolecules & therapeutics, 27(3), 311-317 (2018-10-20)
Mast cells are the most prominent effector cells of Type 1 hypersensitivity immune responses. CYC116 [4-(2-amino-4-methyl-1,3-thiazol-5-yl)-N-[4-(morpholin-4-yl)phenyl] pyrimidin-2-amine] is under development to be used as an anti-cancer drug, but the inhibitory effects of CYC116 on the activation of mast cells and
Ryan P Hobbs et al.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 25(3), 990-1001 (2010-12-16)
Darier's disease (DD) is an inherited autosomal-dominant skin disorder characterized histologically by loss of adhesion between keratinocytes. DD is typically caused by mutations in sarcoendoplasmic reticulum Ca(2+)-ATPase isoform 2 (SERCA2), a major regulator of intracellular Ca(2+) homeostasis in the skin.
Jonathan Martinez-Fabregas et al.
Cell reports, 33(12), 108545-108545 (2020-12-29)
Cytokines are highly pleiotropic ligands that regulate the immune response. Here, using interleukin-6 (IL-6) as a model system, we perform detailed phosphoproteomic and transcriptomic studies in human CD4+ T helper 1 (Th-1) cells to address the molecular bases defining cytokine
Eytan Breman et al.
Frontiers in immunology, 9, 2940-2940 (2019-01-09)
Chimeric Antigen Receptor (CAR) T cells expressing the fusion of the NKG2D protein with CD3ζ (NKG2D-CAR T Cells) acquire a specificity for stress-induced ligands expressed on hematological and solid cancers. However, these stress ligands are also transiently expressed by activated
Saumya Shah et al.
EBioMedicine, 71, 103557-103557 (2021-08-30)
The mycobiome is the fungal component of the gut microbiome and is implicated in several autoimmune diseases. However, its role in MS has not been studied. In this case-control observational study, we performed ITS sequencing and characterised the gut mycobiome
Yasuyoshi Sato et al.
Clinical & translational immunology, 9(10), e1194-e1194 (2020-10-27)
A better understanding of antitumor immunity will help predict the prognosis of gastric cancer patients and tailor the appropriate therapies in each patient. Therefore, we propose a novel immunological classification of gastric cancer. We performed whole-exome sequencing (WES), RNA-Seq and
Jorge A Aguilar-Pineda et al.
iScience, 24(9), 102993-102993 (2021-09-11)
Despite the emerging evidence implying early vascular contributions to neurodegenerative syndromes, the role of vascular smooth muscle cells (VSMCs) in the pathogenesis of Alzheimer disease (AD) is still not well understood. Herein, we show that VSMCs in brains of patients
Andreas Kyburz et al.
The Journal of allergy and clinical immunology, 143(4), 1496-1512 (2018-09-22)
Transmaternal exposure to tobacco, microbes, nutrients, and other environmental factors shapes the fetal immune system through epigenetic processes. The gastric microbe Helicobacter pylori represents an ancestral constituent of the human microbiota that causes gastric disorders on the one hand and
Adeleye Opejin et al.
Cell reports, 33(8), 108424-108424 (2020-11-26)
Various processes induce and maintain immune tolerance, but effector T cells still arise under minimal perturbations of homeostasis through unclear mechanisms. We report that, contrary to the model postulating primarily tolerogenic mechanisms initiated under homeostatic conditions, effector programming is an integral
Sam Sheppard et al.
Cell reports, 35(9), 109210-109210 (2021-06-03)
Natural killer (NK) cells are cytotoxic lymphocytes capable of rapid cytotoxicity, cytokine secretion, and clonal expansion. To sustain such energetically demanding processes, NK cells must increase their metabolic capacity upon activation. However, little is known about the metabolic requirements specific
Katherine M Still et al.
PLoS pathogens, 16(10), e1009027-e1009027 (2020-10-28)
It is of great interest to understand how invading pathogens are sensed within the brain, a tissue with unique challenges to mounting an immune response. The eukaryotic parasite Toxoplasma gondii colonizes the brain of its hosts, and initiates robust immune
Changsong Yang et al.
Nature cell biology, 21(5), 603-613 (2019-04-17)
Mitochondrial fission involves the preconstriction of an organelle followed by scission by dynamin-related protein Drp1. Preconstriction is facilitated by actin and non-muscle myosin II through a mechanism that remains unclear, largely due to the unknown cytoskeletal ultrastructure at mitochondrial constrictions.
Ryan K Alexander et al.
eLife, 9 (2020-05-13)
Metabolic pathways and inflammatory processes are under circadian regulation. Rhythmic immune cell recruitment is known to impact infection outcomes, but whether the circadian clock modulates immunometabolism remains unclear. We find that the molecular clock Bmal1 is induced by inflammatory stimulants
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