Nature reviews. Immunology, Journal Year: 2017, Volume and Issue: 18(2), P. 121 - 133
Published: Oct. 30, 2017
Language: Английский
Immunity, Journal Year: 2015, Volume and Issue: 42(2), P. 216 - 226
Published: Feb. 1, 2015
Language: Английский
Citations
531
Nature Immunology, Journal Year: 2019, Volume and Issue: 20(8), P. 970 - 979
Published: June 24, 2019
Language: Английский
Citations
530
Frontiers in Immunology, Journal Year: 2017, Volume and Issue: 8
Published: April 24, 2017
Il1rl1 (also known as ST2) is a member of the IL-1 superfamily and its only ligand IL-33. ST2 exists in two forms splice variants: soluble form (sST2), which acts decoy receptor, sequesters free IL-33, does not signal, membrane bound (ST2), activates MyD88/NF-κB signaling pathway to enhance mast cell, Th2, regulatory T cell (Treg), innate lymphoid type 2 (ILC2) functions. sST2 levels are increased patients with active inflammatory bowel disease, acute cardiac small transplant allograft rejection, colon gastric cancers, gut mucosal damage during viral infection, pulmonary heart graft-versus-host disease (GVHD). Recently, has been shown be secreted by intestinal pro-inflammatory cells inflammation; on contrary, protective expressing Tregs decreased, implicating that ST2/IL-33 may play an important role disease. This review will focus what various states highlight potential avenues intervene treatment options.
Language: Английский
Citations
522
Cellular and Molecular Gastroenterology and Hepatology, Journal Year: 2017, Volume and Issue: 4(1), P. 33 - 46
Published: March 23, 2017
The intestinal epithelium can be easily disrupted during gut inflammation as seen in inflammatory bowel disease (IBD), such ulcerative colitis or Crohn's disease. For a long time, research into the pathophysiology of IBD has been focused on immune cell–mediated mechanisms. Recent evidence, however, suggests that might play major role development and perpetuation IBD. It is now clear triggered by disturbances epithelial barrier integrity via dysfunctions cell–intrinsic molecular circuits control homeostasis, renewal, repair cells. healthy individual represents semi-permeable physical shielding interior body from invasions pathogens one hand allowing selective passage nutrients other hand. However, must considered much more than simple barrier. Instead, highly dynamic tissue responds to plenitude signals including microbiota system. This response these regulates function, composition microbiota, mucosal homeostasis within lamina propria. thus regarded translator between system aberrant signal transduction adjacent cells promote dysregulation review summarizes important cellular components emphasizes mechanisms leading dysfunction inflammation. SummaryIntestinal defects are frequently article highlights lead disruption promoting diseases. Intestinal intestine meet lifelong service proper food digestion nutrient absorption; this responsibility for import outside inside not without challenges. tract exposed plethora food-borne antigens bacterial microbiota. At same time harbors large part whose task identify fight off foreign microbial threats. cell layer prevents excessive contact with thereby also protects unwanted reactions. achieved sophisticated organization epithelium, which establishes tightly regulated barrier.1Mandel L.J. Bacallao R. Zampighi G. Uncoupling "fence" paracellular "gate" functions tight junctions.Nature. 1993; 361: 552-555Crossref PubMed Scopus (0) Google Scholar built monolayered columnar connected junctions (TJs).2Ivanov A.I. Structure regulation junctions: current concepts unanswered questions.Adv Exp Med Biol. 2012; 763: 132-148PubMed Although TJs barrier, specialized (IECs), goblet Paneth cells, take over miscellaneous antimicrobial defense, make them crucial parts innate Goblet secrete variety molecules, trefoil factors mucins.3McCauley H.A. Guasch Three cheers cell: maintaining epithelia.Trends Mol Med. 2015; 21: 492-503Abstract Full Text PDF Mucin secretion constitutes thick mucus prevent direct bacteria surface protect against invasive pathogens. professional producers peptides, secreted crypts small intestine.4Kopp Z.A. Jain U. Van Limbergen J. et al.Do peptides complement collaborate mucosa?.Front Immunol. 6: 17Crossref (5) controlled antigen delivery plays an education instance, M (microfold)-cells, abundant follicle-associated but appear along crypt-villous axis, up microbes their forward resident gut-associated lymphoid tissue, supporting maturation system.5Ohno H. cells.J Biochem. 2016; 159: 151-160Crossref (114) Thus rather strict gate controlling admission serve host's health. Epithelial challenged high rate turnover. completely renewed only 4–5 days shedding lumen at proliferation stem crypt replacing constant loss.6van der Flier L.G. Clevers Stem self-renewal, differentiation epithelium.Annu Rev Physiol. 2009; 71: 241-260Crossref (623) A failure coordinated replenishment cause severe invasion luminal inflammation, patients (UC) (CD). experimental evidence indeed implicates function onset (IBD). focuses maintenance In steady state maintained shedding. its structural organization, functions, ratio death. 3-dimensional structure characterized invaginations denoted Lieberkühn merging protrusions termed villi. villi lacking resulting flat surface. base give rise fast cycling progenitor migrate toward villus tip while they differentiate mature types. Finally, once reaching colon, IECs shed replaced neighboring Because have limited lifespan about days, constantly replenished enabled multipotent reside base. divide, giving transit-amplifying very proliferative capacity. were first identified several groups 1970s after using H3-thymidine label track proliferating populations.7Cheng Leblond C.P. Origin, renewal four main types mouse intestine. V. Unitarian Theory origin types.Am J Anat. 1974; 141: 537-561Crossref Scholar, 8Potten C.S. Extreme sensitivity some X gamma irradiation.Nature. 1977; 269: 518-521Crossref During last decade especially group Hans Clever's elegantly refined fate mapping creating mouse-model lineage trace candidate marker actively dividing where intermingled These studies ultimately led identification specific leucine rich repeat containing G-protein coupled receptor-5 (Lgr5).9Barker N. van Es J.H. Kuipers al.Identification colon gene Lgr5.Nature. 2007; 449: 1003-1007Crossref (2104) Since then, potential markers vivo linage tracing transgenic fluorescent labelling residing either region +4 position (fourth center) crypt. located directly above described quiescent, reserve populations, reactivated under physiological conditions, injury.10Barker Adult cells: critical drivers regeneration.Nat Cell 2014; 15: 19-33Crossref (200) thought provide steric force moves axis. While migrating upward start various secretory absorptive type.11Noah T.K. Donahue B. Shroyer N.F. differentiation.Exp Res. 2011; 317: 2702-2710Crossref depends death, balance differentiating IECs. warranted microenvironment reside, defined niche. Within niche, IECs, mesenchymal signaling molecules determine differentiation. special expression gives concentration gradient preservation 4 most regulating niche Wnt, Notch, bone morphogenic proteins (BMPs), hedgehog (Figure 1).12Vanuytsel T. Senger S. Fasano A. al.Major pathways cells.Biochim Biophys Acta - Gen Subj. 2013; 1830: 2410-2426Crossref (16) Wnt ligands produced target leads activation canonical noncanonical pathway.13Krausova M. Korinek adult cancer.Cell Signal. 26: 570-579Crossref Canonical drives mainly concentrated lower crypt, located.14Komiya Y. Habas pathways.Organogenesis. 2008; 4: 68-75Crossref extends transit amplifying area rapidly progenies reside. sharp contrast, predominantly observed upper ceases becomes important. frizzled (Fz)-receptors was precisely studied Gregorieff al,15Gregorieff Pinto D. Begthel al.Expression Pattern intestine.Gastroenterology. 2005; 129: 626-638Abstract (309) who revealed strong Wnt3 Wnt9b receptors Fz5 Fz7 activating pathway. accumulation β-catenin subsequently transcription genes govern myofibroblasts.16Kabiri Z. Greicius Madan al.Stroma provides absence Wnts.Development. 2206-2215Crossref (55) Myofibroblasts express Wnt2b, Wnt4, Wnt5, pathway, driving polarity motility therefore IECs.17Sugimura Li L. Noncanonical vertebrate development, diseases.Birth Defects Res C Embryo Today. 2010; 90: 243-256Crossref (73) Fz activate signaling, pathway negatively antagonistic mechanisms, Fz-related proteins.18Bovolenta P. Esteve Ruiz J.M. al.Beyond inhibition: new Frizzled-related disease.J Sci. 121: 737-746Crossref (316) 19Gustafson C.T. Mamo Maran al.Molecular strategies modulating signaling.Front Biosci (Landmark Ed). 2017; 22: 137-156Crossref Secreted close proximity Wnt-producing regulate signalling.15Gregorieff Another protein family BMPs, belong transforming growth factor-β superfamily.20Zhang BMP regulation.Dev 284: 1-11Crossref (125) BMPs throughout crypt-villus antagonists, Noggin, found expressed myofibroblasts crypt.21Batts L.E. Polk D.B. Dubois R.N. al.Bmp required morphogenesis.Dev Dyn. 2006; 235: 1563-1570Crossref (66) contrast ligands, increases axis.22He X.C. Zhang Tong W.G. al.BMP inhibits self-renewal through suppression Wnt–β-catenin signaling.Nat Genet. 2004; 36: 1117-1121Crossref Conditional deletion type I receptor Bmpr1a mice resulted disturbed regeneration increase populations conclusion essential warrant self-renewal.22He One decisions made commitment lineage. decision seems Notch compartment (members Delta Serrate/Jagged subfamilies) cells.23VanDussen K.L. Carulli A.J. Keeley T.M. al.Notch modulates cells.Development. 139: 488-497Crossref (143) Several given model how 2 lineages organized: if 1 expresses notch ligand Delta1, Notch-responsive genes, Hes1 Hes5. master regulators IEC fate. Interestingly, Delta1 linage, inhibiting become secretory, known lateral inhibition.24Crosnier C. Stamataki Lewis Organizing intestine: combinatorial control.Nat 7: 349-359Crossref (391) inhibition warrants both lineages. recent indicated cytokines.25Shang Smith Hu X. Role immunity health disease.Protein Cell. 159-174Crossref (8) example, interleukin (IL) 33 shown down-regulate contributors it indicates immune-epithelial crosstalk central mechanism host defence.26Mahapatro Foersch Hefele al.Programming IL-33 derived pericryptal fibroblasts systemic infection.Cell Rep. 1743-1756Abstract Mesenchymal vicinity niche-promoting dependent signaling. Hedgehog Indian sonic hedgehog, bind Patched cells.6van Paracrine expansion overall because support axis.27Büller N.V.J.A. Rosekrans S.L. Westerlund al.Hedgehog epithelium.Physiology. 27: 148-155Crossref Collectively, milieu Disturbances breakdown finally undesired activity, formation tumors. Maintenance requires epithelium. disposal less rate. Of note, apoptosis necrosis steady-state low caspases villous tip, already process connection death still fully understood, evidences implicate does require caspase consequence process. Recently, significant progress understanding Watson al28Kiesslich Goetz Angus E.M. gaps human confocal endomicroscopy.Gastroenterology. 133: 1769-1778Abstract (130) 29Watson A.J.M. Chu Sieck al.Epithelial sustained despite layers.Gastroenterology. 902-912Abstract used multiphoton microscopy demonstrate expulsed leaving gap state, do compromise sealed TJ occludin TJ-associated scaffolding zonula occludens-1. Further investigations showed expulsion carried out pattern mechanisms: step rearrangement adherens cytoskeletal around basolateral membranes initiated. Rho-associated kinase, myosin light chain kinase (MLCK) dynamin II build tension pushed lumen.30Marchiando A.M. Shen Graham W.V. al.The junction pathologic shedding.Gastroenterology. 140: 1208-1218Abstract Meanwhile occludin, capture space, connect Considering endoscopic view patient suffering acute flare, obvious there observation question whether As discussed following, lines underline defect alone suffices develop Besides even microscopic strongly supports impression revealing decrease cells31Pullan R.D. Thomas G.A. Rhodes al.Thickness adherent gel colonic mucosa humans relevance colitis.Gut. 1994; 35: 353-359Crossref (342) Scholar; defective defensin production32Courth L.F. Ostaff M.J. Mailänder-Sánchez al.Crohn's disease-derived monocytes fail induce defensins.Proc Natl Acad 112: 14000-14005Crossref reduced thickness layer; altered regard mucins, phosphatidylcholine, glycosylation.33Wehkamp Koslowski Wang al.Barrier due distinct deficiencies disease.Mucosal 1: S67-S74Crossref addition, associated dysbiosis itself result increased permeability.34Fava F. disease: Friend foe?.World Gastroenterol. 17: 557Crossref Indirect data suggest precede includes fact quiescent permeability.35Vivinus-Nébot Frin-Mathy Bzioueche al.Functional symptoms diseases: low-grade inflammation.Gut. 63: 744-752Crossref (68) Furthermore, 40% first-degree relatives CD show permeability.36Hollander Vadheim C.M. Brettholz E. al.Increased permeability relatives. possible etiologic factor.Ann Intern 1986; 105: 883-885Crossref 37May G.R. Sutherland L.R. Meddings J.B. Is really disease?.Gastroenterology. 104: 1627-1632Abstract 38Munkholm Langholz Hollander al.Intestinal degree relatives.Gut. 68-72Crossref 39Peeters Geypens Claus al.Clustering families disease.Gastroenterology. 1997; 113: 802-807Abstract 40Russell Satsangi IBD: affair.Best Pract Clin 18: 525-539Abstract 41Fries W. Renda M.C. Lo Presti M.A. genetic determinants patients, relatives, controls high-incidence Southern Italy.Am 100: 2730-2736Crossref no overt IBD, long-term follow-up currently available, difficult impact permeability. There study relative impaired evaluation developed ileocolonic years after.42Irvine E.J. Marshall J.K. Increased precedes subject familial risk.Gastroenterology. 2000; 119: 1740-1744Abstract often subclinical measuring fecal calprotectin concentrations, represent neutrophil flux intestine, significantly levels compared subjects.43Thjodleifsson Sigthorsson Cariglia al.Subclinical inflammation: inherited abnormality relatives?.Gastroenterology. 2003; 124: 1728-1737Abstract 44Montalto Curigliano Santoro al.Fecal colitis.Am 102: 132-136Crossref Additionally, asymptomatic higher basal cytokines, IL2, IL6, IL8, subjects.45Indaram A.V. Nandi Weissman al.Elevated cytokine disease.World 49-52Crossref initiated virtue environmental triggers. Such substances sodium caprate (an ingredient milk fat) acetylsalicylic acid act noninflamed CD, permeability.46Söderholm J.D. Olaison Peterson K.H. al.Augmented stimuli non-inflamed ileum disease.Gut. 2002; 50: 307-313Crossref 47Zamora S.A. Hilsden R.J. before ibuprofen children disease.Can 1999; 13: 31-36Crossref 48Hilsden Sutherl
Language: Английский
Citations
513
Nature reviews. Immunology, Journal Year: 2017, Volume and Issue: 18(2), P. 121 - 133
Published: Oct. 30, 2017
Language: Английский
Citations
508