Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer’s disease

Nature Neuroscience, Год журнала: 2019, Номер 22(3), С. 401 - 412

Опубликована: Фев. 11, 2019

Язык: Английский

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IFNγ: signalling, epigenetics and roles in immunity, metabolism, disease and cancer immunotherapy

Nature reviews. Immunology, Год журнала: 2018, Номер 18(9), С. 545 - 558

Опубликована: Июнь 19, 2018

Язык: Английский

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IL-10 Family Cytokines IL-10 and IL-22: from Basic Science to Clinical Translation

Immunity, Год журнала: 2019, Номер 50(4), С. 871 - 891

Опубликована: Апрель 1, 2019

Язык: Английский

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Biology and therapeutic potential of interleukin-10

The Journal of Experimental Medicine, Год журнала: 2019, Номер 217(1)

Опубликована: Окт. 14, 2019

The cytokine IL-10 is a key anti-inflammatory mediator ensuring protection of host from over-exuberant responses to pathogens and microbiota, while playing important roles in other settings as sterile wound healing, autoimmunity, cancer, homeostasis. Here we discuss our current understanding the regulation production molecular pathways associated with responses. In addition IL-10’s classic inhibitory effects on myeloid cells, also describe nonclassic attributed this pleiotropic cytokine, including how regulates basic processes neural adipose cells it promotes CD8 T cell activation, well epithelial repair. We further its therapeutic potential context different diseases outstanding questions that may help develop an effective application diverse clinical settings.

Язык: Английский

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Inflammasome activation and regulation: toward a better understanding of complex mechanisms

Cell Discovery, Год журнала: 2020, Номер 6(1)

Опубликована: Июнь 8, 2020

Inflammasomes are cytoplasmic multiprotein complexes comprising a sensor protein, inflammatory caspases, and in some but not all cases an adapter protein connecting the two. They can be activated by repertoire of endogenous exogenous stimuli, leading to enzymatic activation canonical caspase-1, noncanonical caspase-11 (or equivalent caspase-4 caspase-5 humans) or caspase-8, resulting secretion IL-1β IL-18, as well apoptotic pyroptotic cell death. Appropriate inflammasome is vital for host cope with foreign pathogens tissue damage, while aberrant cause uncontrolled responses that may contribute various diseases, including autoinflammatory disorders, cardiometabolic cancer neurodegenerative diseases. Therefore, it imperative maintain fine balance between inhibition, which requires fine-tuned regulation assembly effector function. Recently, growing body studies have been focusing on delineating structural molecular mechanisms underlying signaling. In present review, we summarize most recent advances remaining challenges understanding ordered upon sensing diverse tight regulations these processes. Furthermore, review progress translating research into therapeutic tools, aimed at modifying inflammasome-regulated human

Язык: Английский

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Macrophages in intestinal inflammation and resolution: a potential therapeutic target in IBD

Nature Reviews Gastroenterology & Hepatology, Год журнала: 2019, Номер 16(9), С. 531 - 543

Опубликована: Июль 16, 2019

Язык: Английский

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New insights into the interplay between autophagy, gut microbiota and inflammatory responses in IBD

Autophagy, Год журнала: 2019, Номер 16(1), С. 38 - 51

Опубликована: Июль 9, 2019

One of the most significant challenges inflammatory bowel disease (IBD) research is to understand how alterations in symbiotic relationship between genetic composition host and intestinal microbiota, under impact specific environmental factors, lead chronic inflammation. Genome-wide association studies, followed by functional have identified a role for numerous autophagy genes IBD, especially Crohn disease. Studies using vitro vivo models, addition human clinical studies revealed that pivotal homeostasis maintenance, gut ecology regulation, appropriate immune responses anti-microbial protection. This review describes latest researches on mechanisms which dysfunctional leads disrupted epithelial function, dysbiosis, defect peptide secretion Paneth cells, endoplasmic reticulum stress response aberrant pathogenic bacteria. A better understanding IBD pathogenesis may provide sub-classification phenotypes novel approaches management.Abbreviations: AIEC: adherent-invasive Escherichia coli; AMPK: AMP-activated protein kinase; ATF6: activating transcription factor 6; ATG: related; Atg16l1[ΔIEC] mice: mice with Atg16l1 depletion specifically cells; Atg16l1[HM] hypomorphic expression; BCL2: B cell leukemia/lymphoma 2; BECN1: beclin 1, CALCOCO2: calcium binding coiled-coil domain CASP: caspase; CD: disease; CGAS: cyclic GMP-AMP synthase; CHUK/IKKA: conserved helix-loop-helix ubiquitous CLDN2: claudin DAPK1: death associated kinase 1; DCs: dendritic DSS: dextran sulfate sodium; EIF2A: eukaryotic translation initiation 2A; EIF2AK: 2 alpha ER: reticulum; ERBIN: Erbb2 interacting protein; ERN1/IRE1A: ER nucleus signaling FNBP1L: formin 1-like; FOXP3: forkhead box P3; GPR65: G-protein coupled receptor 65; GSK3B: glycogen synthase 3 beta; IBD: IECs: IFN: interferon; IL: interleukin; IL10R: interleukin 10 receptor; IRGM: immunity related GTPase M; ISC: stem cell; LAMP1: lysosomal-associated membrane LAP: LC3-associated phagocytosis; MAP1LC3B: microtubule-associated 1 light chain LPS: lipopolysaccharide; LRRK2: leucine-rich repeat MAPK: mitogen-activated MHC: major histocompatibility complex; MIF: macrophage migration inhibitory factor; MIR/miRNA: microRNA; MTMR3: myotubularin 3; MTOR: mechanistic target rapamycin MYD88: myeloid differentiation primary gene 88; NLRP3: NLR family, pyrin containing NOD2: nucleotide-binding oligomerization NPC: Niemann-Pick type C; NPC1: NPC intracellular cholesterol transporter OMVs: outer vesicles; OPTN: optineurin; PI3K: phosphoinositide 3-kinase; PRR: pattern-recognition PTPN2: tyrosine phosphatase, non-receptor PTPN22: 22 (lymphoid); PYCARD/ASC: PYD CARD containing; RAB2A: RAB2A, member RAS oncogene family; RELA: v-rel reticuloendotheliosis viral homolog (avian); RIPK2: (TNFRSF)-interacting serine-threonine ROS: reactive oxygen species; SNPs: single nucleotide polymorphisms; SQSTM1: sequestosome TAX1BP1: Tax1 Th: T helper TIRAP/TRIF: toll-interleukin (TIR) domain-containing adaptor TLR: toll-like TMEM173/STING: transmembrane 173; TMEM59: 59; TNF/TNFA: tumor necrosis Treg: regulatory T; TREM1: triggering expressed cells UC: ulcerative colitis; ULK1: unc-51 like WT: wild-type; XBP1: X-box XIAP: X-linked inhibitor apoptosis.

Язык: Английский

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Cytokine Networks in the Pathophysiology of Inflammatory Bowel Disease

Immunity, Год журнала: 2019, Номер 50(4), С. 992 - 1006

Опубликована: Апрель 1, 2019

Язык: Английский

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Pathophysiology of Chronic Graft-versus-Host Disease and Therapeutic Targets

New England Journal of Medicine, Год журнала: 2017, Номер 377(26), С. 2565 - 2579

Опубликована: Дек. 28, 2017

Chronic GVHD, an autoimmune disease that follows allogeneic hematopoietic-cell transplantation, is characterized by infections and debilitating tissue injury leading to irreversible fibrosis. Insights into the pathophysiology of are providing new therapeutic targets.

Язык: Английский

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Autophagy in inflammation, infection, and immunometabolism

Immunity, Год журнала: 2021, Номер 54(3), С. 437 - 453

Опубликована: Март 1, 2021

Язык: Английский

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