Cells of the human intestinal tract mapped across space and time

Nature, Год журнала: 2021, Номер 597(7875), С. 250 - 255

Опубликована: Сен. 8, 2021

Abstract The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing response to functional requirements environmental exposures. Here, comprehensively map cell lineages, we use single-cell RNA sequencing antigen receptor analysis almost half a million cells from up 5 anatomical regions 11 distinct healthy paediatric adult gut. This reveals existence transcriptionally BEST4 epithelial tract. Furthermore, implicate IgG sensing as function tuft cells. We describe neural populations enteric nervous system, predict cell-type-specific expression genes associated with Hirschsprung’s disease. Finally, using systems approach, identify key players that drive formation secondary lymphoid tissue early development. show these programs are adopted inflammatory bowel disease recruit retain immune at site inflammation. catalogue will provide new insights into development, homeostasis

Язык: Английский

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Mucins in Intestinal Mucosal Defense and Inflammation: Learning From Clinical and Experimental Studies

Frontiers in Immunology, Год журнала: 2020, Номер 11

Опубликована: Сен. 4, 2020

Throughout the gastrointestinal (GI) tract, a distinct mucus layer composed of highly glycosylated proteins called mucins plays essential roles in providing lubrication for passage food, participating cell signaling pathways and protecting host epithelium from commensal microorganisms invading pathogens, as well toxins other environmental irritants. These can be broadly classified into either secreted gel-forming mucins, those that provide structural backbone barrier, or transmembrane form glycocalyx covering underlying epithelial cells. Goblet cells dispersed among intestinal are chiefly responsible synthesis secretion within gut heavily influenced by interactions with immune system. Evidence both clinical animal studies have indicated several GI conditions, including inflammatory bowel disease (IBD), colorectal cancer, numerous enteric infections accompanied considerable changes mucin quality quantity. include, but not limited to, impaired goblet function, dysregulation altered post-translational modifications. The current review aims to highlight functional features production immunological regulation impact these key elements context barrier function defense inflammation.

Язык: Английский

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Pathophysiology of Inflammatory Bowel Disease: Innate Immune System

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(2), С. 1526 - 1526

Опубликована: Янв. 12, 2023

Inflammatory bowel disease (IBD), comprising Crohn’s (CD) and ulcerative colitis (UC), is a heterogeneous state of chronic intestinal inflammation with no exact known cause. Intestinal innate immunity enacted by neutrophils, monocytes, macrophages, dendritic cells (DCs), lymphoid NK cells, characterized their capacity to produce rapid nonspecific reaction as first-line response. Innate immune (IIC) defend against pathogens excessive entry microorganisms, while preserving tolerance resident microbiota. Changes this equilibrium are linked in the gut IBD. IICs mediate host defense responses, inflammation, tissue healing producing cytokines chemokines, activating complement cascade phagocytosis, or presenting antigens activate adaptive exert important functions that promote ameliorate cellular molecular mechanisms underlie sustain A comprehensive understanding underlying these clinical manifestations will be for developing therapies targeting system IBD patients. This review examines complex roles interactions among IICs, other non-immune homeostasis pathological conditions.

Язык: Английский

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Paradoxical gastrointestinal effects of interleukin-17 blockers

Annals of the Rheumatic Diseases, Год журнала: 2020, Номер 79(9), С. 1132 - 1138

Опубликована: Июль 21, 2020

Secukinumab, ixekizumab and brodalumab are monoclonal antibody therapies that inhibit interleukin (IL)-17 activity widely used for the treatment of psoriasis, psoriatic arthritis ankylosing spondylitis. The promising efficacy results in dermatology rheumatology prompted evaluation these drugs Crohn's disease ulcerative colitis, but onset paradoxical events (disease exacerbation after with a theoretically curative drug) prevented their approval patients inflammatory bowel diseases (IBDs). To date, pathophysiological mechanisms underlying effects not well defined, there no clear guidelines management flare or new IBD anti-IL-17 drug therapy. In this review, we summarise literature on putative mechanisms, clinical digestive therapy IL-17 inhibitors provide guidance practice.

Язык: Английский

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Single-cell atlas of colonic CD8+ T cells in ulcerative colitis

Nature Medicine, Год журнала: 2020, Номер 26(9), С. 1480 - 1490

Опубликована: Авг. 3, 2020

Язык: Английский

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Early-life interactions between the microbiota and immune system: impact on immune system development and atopic disease

Nature reviews. Immunology, Год журнала: 2023, Номер 23(11), С. 735 - 748

Опубликована: Май 3, 2023

Язык: Английский

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Role of the IL23/IL17 Pathway in Crohn’s Disease

Frontiers in Immunology, Год журнала: 2021, Номер 12

Опубликована: Март 30, 2021

Crohn’s disease (CD) is a chronic relapsing disorder of the gastrointestinal tract and represents one main entities inflammatory bowel (IBD). CD affects genetically susceptible patients that are influenced by environmental factors intestinal microbiome, which results in excessive activation mucosal immune system aberrant cytokine responses. Various studies have implicated pro-inflammatory cytokines IL17 IL23 pathogenesis CD. member IL12 family able to enhance affect expansion pathogenic T helper type 17 (Th17) cells through various mechanisms, including maintenance Th17 signature genes, upregulation effector genes or suppression repressive factors. Moreover, signaling induce cascade molecules like TNF, IFNγ, IL22, lymphotoxin, IL1β lipopolysaccharide (LPS). Here, IL17A TNF known mediate synergistically drive expression genes. Recent advances understanding immunopathogenetic mechanisms underlying led development new biological therapies selectively intervene inhibit processes caused mediators IL23. Recently published data demonstrate treatment with selective inhibitors lead markedly high response rates cohort failed previous anti-TNF therapy. Macrophages considered as source intestine supposed play key role molecular crosstalk cell subsets innate lymphoid gut. The following review focuses on pathways specific IL23/IL17 pathway.

Язык: Английский

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Ketogenic diet alleviates colitis by reduction of colonic group 3 innate lymphoid cells through altering gut microbiome

Signal Transduction and Targeted Therapy, Год журнала: 2021, Номер 6(1)

Опубликована: Апрель 23, 2021

Abstract Accumulating evidence suggests that ketogenic diets (KDs) mediate the rise of circulating ketone bodies and exert a potential anti-inflammatory effect; however, consequences this unique diet on colitis remain unknown. We performed series systematic studies using dextran sulfate sodium (DSS) animal model inflammatory colitis. Animals were fed with KD, low-carbohydrate (LCD), or normal (ND). Germ-free mice utilized in validation experiments. Colon tissues analyzed by transcriptome sequencing, RT2 profiler PCR array, histopathology, immunofluorescence. Serum samples metabolic assay kit. Fecal 16S rRNA gene liquid chromatography–mass spectrometry gas spectrometry. observed KD alleviated altering gut microbiota metabolites manner distinct from LCD. Quantitative experiments confirmed impact relative to LCD reproducible increase Akkermansia , whereas opposite was for Escherichia/Shigella . After induction, protected intestinal barrier function, reduced production RORγt + CD3 − group 3 innate lymphoid cells (ILC3s) related cytokines (IL-17α, IL-18, IL-22, Ccl4). Finally, fecal transplantation into germ-free revealed KD- mediated inhibition ILC3 regulation dependent modification microbiota. Taken together, our study presents global view microbiome-metabolomics changes occur during treatment, identifies microbiome ILC3s as novel targets involving IBD dietary therapy.

Язык: Английский

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Innate Lymphoid Cells in Intestinal Homeostasis and Inflammatory Bowel Disease

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(14), С. 7618 - 7618

Опубликована: Июль 16, 2021

Inflammatory bowel disease (IBD) is a heterogeneous state of chronic intestinal inflammation unknown cause encompassing Crohn’s (CD) and ulcerative colitis (UC). IBD has been linked to genetic environmental factors, microbiota dysbiosis, exacerbated innate adaptive immunity epithelial barrier dysfunction. classically associated with gut accumulation proinflammatory Th1 Th17 cells accompanied by insufficient Treg numbers Tr1 immune suppression. T guide perpetuate constant hypersensitivity microbial antigens, tissue injury inflammation. Recent studies mucosal homeostasis suggest involvement lymphoid (ILCs). These lymphoid-origin are counterparts but lack the antigen receptors expressed on B cells. ILCs play important roles in first line antimicrobial defense contribute organ development, protection regeneration, maintaining balance between antipathogen commensal tolerance. Intestinal requires strict regulation quantity activity local ILC subpopulations. demonstrated that changes during development. A better understanding behavior gastrointestinal will provide valuable insights into new approaches treatment. This review summarizes recent research latest advances role IBD, particular emphasis interaction populations functions.

Язык: Английский

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Bile Acid–Gut Microbiota Axis in Inflammatory Bowel Disease: From Bench to Bedside

Nutrients, Год журнала: 2021, Номер 13(9), С. 3143 - 3143

Опубликована: Сен. 9, 2021

Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract, with increasing prevalence, and its pathogenesis remains unclear. Accumulating evidence suggested that gut microbiota bile acids play pivotal roles in intestinal homeostasis inflammation. Patients IBD exhibit decreased microbial diversity abnormal composition marked by depletion phylum Firmicutes (including bacteria involved acid metabolism) enrichment Proteobacteria. Dysbiosis leads to blocked transformation. Thus, concentration primary conjugated elevated at expense secondary IBD. In turn, could modulate community. Gut dysbiosis disturbed impair barrier immunity. Several therapies, such as diets, probiotics, prebiotics, engineered bacteria, fecal transplantation ursodeoxycholic acid, may alleviate restoring acids. acid-gut axis closely connected pathogenesis. Regulation this be novel option for treating

Язык: Английский

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